bluuebunny/crossref_metadata_2025 huggingface dataset:
Prática de governança e gestão técnica da assistência farmacêutica no Município de Xinguara, Pará
Authors: Ferreira Renata Lima , Soler Orenzio
Published: April 2021

Objetivo: Investigar a prática de governança e gestão técnica da assistência farmacêutica no município de Xinguara, Pará. Métodos: Trata-se de um estudo de caso, ocorrido entre julho de 2018 e junho de 2019, fundamentado na Pesquisa-Ação e na Triangulação de Métodos, sobre o processo de governança e gestão técnica da assistência farmacêutica. Resultados: Apresenta-se evidências sobre tipos de intervenções que asseguram uma melhor qualidade da assistência farmacêutica, os desfechos da oficina  de planejamento estratégico situacional, o cumprimento de indicadores relacionados as práticas de governança, indicadores relacionados instrumentos de planejamento e gestão, gestão técnica da assistência farmacêutica, gestão clínica do medicamento, políticas setoriais e cumprimento de indicadores relacionados a logística da assistência farmacêutica. Conclusão: Infere-se a necessidade do planejamento municipal explicitar as ações de assistência farmacêutica articuladas à coordenação técnica de assistência farmacêutica e vinculadas aos instrumentos de gestão. Preconiza-se intervenções farmacêuticas que fortaleçam a governança e a gestão técnica da assistência farmacêutica no município de Xinguara, Pará.
Alterações bucais e sistêmicas da Histiocitose de Células de Langerhans em paciente pediátrico: Relato de caso
Authors: Cabral Chauí de Lima , Souza Nayron Lourenço Ivo de , Cunha Romário Dias da , Soares Ana Larissa Fernandes de Holanda
Published: April 2021

A Histiocitose de Células de Langerhans (LCH) é uma desordem associada à proliferação das células de Langerhans. Devido à sua natureza infiltrativa, a LCH pode envolver órgãos como a pele, os gânglios, o pulmão e o fígado. Estima-se que sua incidência é de aproximadamente 5 a 10 casos em um milhão por ano, principalmente em menores de 15 anos, com predominância no sexo masculino, na proporção de 2:1 e sua patogênese permanece desconhecida. Objetivou-se com este estudo descrever as manifestações sistêmicas e orais da LCH, em uma criança, destacando a importância do cirurgião-dentista no diagnóstico precoce das lesões bucais na atenção básica. Para descrição do caso clínico, as informações foram obtidas por meio de consulta ao prontuário do paciente no Hospital Universitário Onofre Lopes – HUOL. Paciente do sexo masculino, 4 meses, apresentava lesões na cavidade oral em rebordo alveolar inferior, superior e palato duro, exofíticas formada por regiões eritroplásicas e leucoplásicas não removida durante raspagem, com distensão abdominal, fontanela normotensa, presença de “nódulo” cefálico parietal, ictérico, colúria, hipocolia fecal e genitália hiperemiada. Concluímos que a criança possuía quadro clínico compatível com LCH. Este trabalho mostrou ainda a importância do cirurgião-dentista, especialmente na Atenção Básica de saúde, para o correto diagnóstico de doenças sistêmicas, com manifestações bucais, assim como a sua responsabilidade na ordenação do cuidado na busca pela integralidade da atenção.
Spatial and temporal variation in the species diversity of coastal California fish eggs
Authors: Choi ES , Furtado LE , Burton RS
Published: April 2021

Ichthyoplankton studies can be used to assess the abundance, distribution, and reproductive activity of marine fishes, but few studies have monitored spawning activity at inshore sites. This study utilized weekly plankton sampling to construct a year-long time series of fish spawning at 6 pier sites along the California coast—Santa Cruz, San Luis Obispo, Santa Barbara, Santa Monica, Newport Beach, and La Jolla; sampling at the La Jolla site continues ongoing monitoring initiated in 2012. Fish eggs were sorted from the collected plankton and identified to species level using DNA barcoding of the COI and 16S genes. While only one year of data has been collected from 5 of the sites, the 2 sites north of Point Conception show markedly reduced diversity compared to the southern sites. Although the species observed reflect the local environment of each site, this pattern of reduced diversity at the northern sites is consistent with the well-documented decline in species richness with latitude along the California coast. The 7-year time series from La Jolla has revealed that spawning activity varies greatly among years, both in terms of egg production and species diversity, with a continuing trend of highest egg numbers in years with colder average winter sea surface temperature.
Deficits in Visual Processing During Hypoxia as Evidenced by Visual Mismatch Negativity
Authors: Blacker Kara J. , Seech Todd R. , Funke Matthew E. , Kinney Micah J.
Published: April 2021

INTRODUCTION: Hypoxia is an ever-present threat in tactical aviation and gained recent attention due to its putative role in physiological episodes. Previous work has demonstrated that hypoxia negatively impacts a variety of sensory, cognitive, and motor systems. In particular,
the visual system is one of the earliest systems affected by hypoxia. While the majority of previous studies have relied on self-report and behavioral testing, the use of event-related potentials as a novel tool to monitor responses to low oxygen in humans has recently been investigated. Specifically,
ERP components that are evoked passively in response to unattended changes in background sensory stimulation have been explored.METHOD: Subjects (N 28) completed a continuous visuomotor tracking task while EEG was recorded. During the tracking task, a series of standard color
checkerboard patterns were presented in the periphery while occasionally a deviant color checkerboard was presented. The visual mismatch negativity (MMN) component was assessed in response to the deviant compared to the standard stimuli. Subjects completed two sessions in counterbalanced order
that only differed by the oxygen concentration breathed (10.6% vs. 20.4%).RESULTS: Results demonstrated a significant reduction in the amplitude of the visual MMN under hypoxic compared to normoxic conditions, showing a 50% reduction in amplitude during hypoxia. Our results suggest
that during low-oxygen exposure the ability to detect environmental changes and process sensory information is impaired.DISCUSSION: The visual MMN may represent an early and reliable predictor of sensory and cognitive deficits during hypoxia exposure, which may be of great use to
the aviation community.Blacker KJ, Seech TR, Funke ME, Kinney MJ. Deficits in visual processing during hypoxia as evidenced by visual mismatch negativity. Aerosp Med Hum Perform. 2021; 92(5):326332.
Igrifikacijski elementi na mrežnim stranicama enciklopedija
Authors: Mihaljević Josip
Published: April 2021

U radu
se analiziraju igre i igrifikacijski elementi koji se nalaze na mrežnim
stranicama enciklopedija. Analizirano je 92 mrežnih stranica općih i posebnih enciklopedija,
od kojih 14 sadržava obrazovne mrežne igre ili određene igrifikacijske
elemente. Te su igre razvrstane s obzirom na tip: kviz, križaljka, vješala,
slagalica ili zagonetka, jedinstvene igre, igre povezivanja itd. Također su unutar
igara enciklopedija te stranica enciklopedija identificirani igrifikacijski
elementi koji su često prisutni: bodovanje, razine, priča, sustav nagrađivanja
itd. Rezultati provedene analize pokazuju da još uvijek malo mrežnih
enciklopedija sadržava igre i igrifikacijske elemente (15%) te da od
enciklopedija koje imaju igre većina ima kvizove (70%), ali također da postoje
neke jedinstvene obrazovne igre koje sadržavaju priču te mogu pomoći
korisnicima u učenju geografije, činjenica o životinjama itd. Postoje i igre
poput The Wikipedia Adventure, koje
poučavaju korisnike kako se koristiti Wikipedijom.
Istraživanje je provedeno u sklopu projekta Hrvatski
mrežni rječnik – Mrežnik kako bi se osmislio konceptualni okvir igrifikacije
mrežnoga rječnika. Metodologija izrade konceptualnoga okvira e-rječnika uz neke
se preinake može iskoristiti i za izradu konceptualnoga okvira igrifikacije
enciklopedije.
Croatian external relations as reflected by the use of exonyms
Authors: Jordan Peter
Published: April 2021

Departing from the assumption that exonyms, in the sense of »names used in a specific language for a geographical feature situated outside the area where that
language is spoken and differing in its form from the name used in an official
or well-established language of the area where the geographical feature is situated«
(UN Glossary definition 2007), are indicators of external historical as well as
current political, cultural, and economic relations of a community, the article
investigates the case of Croatian exonyms as documented by the recently
published editions of Ivana Crljenko (2016, 2018). For comparison,
(Austrian-)German, Hungarian and Italian exonyms are also examined in this respect.
In essence, the assumption is found to also be confirmed by the Croatian case,
although several linguistic factors distort the picture. The article also
reveals the weaknesses of the current UN Glossary definitions of the terms
»exonym« and »endonym«.
Inverse Intimacy: Reconfiguring ‘Personal Relations’ in Elizabeth Bowen's The Hotel
Authors: Bristow Joseph
Published: April 2021

Ever since its publication in 1927, Elizabeth Bowen's first novel, The Hotel, has prompted critical responses that have tried to gauge the ways in which the narrative represents intimacy between women. Although one of its earliest reviewers sensed that the ‘dark, forlorn spirit of inversion is all through it’, modern critics have acknowledged that The Hotel is not engaged with the sexological models of inversion that inform Radclyffe Hall's contemporaneous novel, The Well of Loneliness (1928). At the same time, commentators have recognized that The Hotel forms part of a group of 1920s fictions that address female homosexuality with increasing openness. For the most part, readers have focused close attention on the intimate friendship that develops between the young Sydney Warren and the middle-aged widow Mrs. Kerr. This bond, even if it is fraught with tension, remains a source of prurient fascination among the other English residents enjoying a wintertime dolce far niente on the Italian Riviera. Still, the sustained critical focus on the attachment that develops between these two characters has tended to ignore the significance of the partnership between the two single women, Miss Pym and Miss Fitzgerald, that places the whole span of the novel in parentheses. Although recent studies by Elizabeth Cullingford and Maud Ellmann have drawn attention to Bowen's interest in what it means to be a ‘singleton’ or part of stadial series of personal relationships (single, couple, and triad), little has been said about the two spinsters, each of whom is ‘half of a duality’. The present essay concentrates attention on the ways in which the enumerative turn in Bowen studies broadens in scope when we look at how Miss Pym and Miss Fitzgerald appear as both two in one and one in two: a narrative formula that reminds us not of sexual inversion but the inverse number in mathematics. It is this type of inverse intimacy between woman and woman that triumphs at the end of The Hotel.
‘as though nothing were happening—or rather, not happening’: Excess and Vacuity in The Little Girls
Authors: Harper Margaret Mills
Published: April 2021

There's a hole in the middle of Bowen's late novel The Little Girls, literally as well as figuratively: a cavity in the ground dug by three childhood friends for the purpose of burying a secret box. Indeed, the novel is full of holes, from caves and missing treasures to absences, losses, and griefs. At the same time, the book displays a fullness or even extravagant overstuffed quality. Its style, pace, plot, and themes are supersatured, with breathless dialogue, restless activity, and suggestive detail. The Little Girls is very funny even as it never wanders far from catastrophe. The novelistic decision to throw the two modes of comedy and tragedy together is one of the many risks Bowen takes in this novel. She does so as part of a larger meditation on the structures that support art as it frames and thus falsifies, but also acknowledges human lives and history. The Little Girls is about emptiness and loss, but it also suggests that the superfluities and distractions with which people fill their lives have value. This essay pursues several strands of intertextual allusions to find something of what the novel both flamboyantly offers and steadfastly refuses.
EVALUATION OF THE CHARACTERISTICS OF REVISITS TO AN ADULT EMERGENCY DEPARTMENT WITHIN 72 HOURS
Authors: Uzun Nedim , Altinbilek Ertuğrul , Sever M. Yaşar , Çalik Mustafa
Published: April 2021

The objective of this study was to determine revisits of the patients discharged from the adult emergency department of our hospital in the early period (72 hours) between January 2016 and December 2016, and to evaluate characteristics of these revisits. In this study, records of the patients discharged from the adult emergency department in 2016 were retrospectively screened from the hospital information management system. Of the 361,413 patients, 7,800 (2.1%) met the inclusion criteria. The most common cause of the initial presentation was unexplained pain with 890 (11.4%) patients, while the most common diagnosis in revisits was acute upper respiratory tract infection with 642 (8.2%) patients. It was found that 18 patients (2.23%) died in the emergency department. No significant difference was found between triage scores of the emergency department presentations, while 161 patients with green area triage in the initial presentation presented to the red area and 134 of these patients were discharged. In our study, the revisit rate was similar with the studies in the literature. It was observed that the majority of the patients who revisited were discharged after the initial visit and they presented to the emergency department again upon their complaints continued. It was thought that revisits can be largely prevented with correct prescription and providing better information to patients.
Utforska representationer banar väg för meningsskapande
Authors: Lunde Torodd
Published: April 2021

Lärare kan skapa progression i lärandet genom aktiviteter där elever får konstruera och utforska innebörden av representationer. Det visar en studie där forskare undersökte hur elever utvecklade sina kunskaper med hjälp av representationer i en undervisningssekvens om människokroppen.
Diginär: Digital exkludering av äldre
Authors: Gustafsson Agnes , Lundén Matilda
Published: April 2021

Om oss
Vi som driver diginär heter Agnes Gustafsson och Matilda Lundén och vi är två studenter på Linköpings universitet som läser sista terminen på kandidatprogrammet “Språk, litteratur och medier”.

Diginär är resultatet av ett projekt där vi fick i uppgift att lyfta ett aktuellt ämne i dagens samhälle. Som vi nämnt i några av våra texter så känner vi att detta är ett problem som är svårt för de berörda att lyfta så de själva inte rör sig på de plattformar där problemet bör diskuteras. Då vi båda har äldre personer i vår närhet som upplever digital exkludering kände vi att det var ett ämne vi vill lyfta för att hjälpa våra mor- och farföräldrar, och alla andra som riskerar att hamna utanför i samhället.

Med våra texter vill vi informera och upplysa allmänheten om detta samhällsproblem så att alla får samma förutsättningar för att utföra vardagliga sysslor i vårt samhälle!

Vill du veta mer om digital exkludering? Läs gärna våra texter och se vår film, eller varför inte slänga iväg en kommentar så att vi kan skapa en diskussion?

Glada hälsningar,

Agnes och Matilda
Mechanoresponsive Smad5 Enhances MiR-487a Processing to Promote Vascular Endothelial Proliferation in Response to Disturbed Flow
Authors: Wang Wei-Li , Chen Li-Jing , Wei Shu-Yi , Shih Yu-Tsung , Huang Yi-Hsuan , Lee Pei-Lin , Lee Chih-I , Wang Mei-Cun , Lee Ding-Yu , Chien Shu , Chiu Jeng-Jiann
Published: April 2021

MicroRNAs (miRs) and bone morphogenetic protein receptor–specific Smads are mechano-responsive molecules that play vital roles in modulating endothelial cell (EC) functions in response to blood flow. However, the roles of interplay between these molecules in modulating EC functions under flows remain unclear. We elucidated the regulatory roles of the interplay between miR-487a and Smad5 in EC proliferation in response to different flow patterns. Microarray and quantitative RT-PCR showed that disturbed flow with low and oscillatory shear stress (OS, 0.5 ± 4 dynes/cm2) upregulates EC miR-487a in comparison to static controls and pulsatile shear stress (12 ± 4 dynes/cm2). MiR-487a expression was higher in ECs in the inner curvature (OS region) than the outer curvature of the rat aortic arch and thoracic aorta and also elevated in diseased human coronary arteries. MiR-487a expression was promoted by nuclear phospho-Smad5, which bound to primary-miR-487a to facilitate miR-487a processing. Algorithm prediction and luciferase reporter and argonaute 2-immunoprecipitation assays demonstrated that miR-487a binds to 3′UTR of CREB binding protein (CBP) and p53. Knockdown and overexpression of miR-487a decreased and increased, respectively, phospho-Rb and cyclin A expressions through CBP and p53. A BrdU incorporation assay showed that miR-487a enhanced EC proliferation under OS in vitro and in disturbed flow regions of experimentally stenosed rat abdominal aorta in vivo. These results demonstrate that disturbed flow with OS induces EC expression of miR-487a through its enhanced processing by activated-Smad5. MiR-487 inhibits its direct targets CBP and p53 to induce EC cycle progression and proliferation. Our findings suggest that EC miR-487 may serve as an important molecular target for intervention against disturbed flow–associated vascular disorders resulting from atherosclerosis.
Microbial Fabricated Nanosystems: Applications in Drug Delivery and Targeting
Authors: Sachin Kumar , Karn Santosh Kumar
Published: April 2021

The emergence of nanosystems for different biomedical and drug delivery applications has drawn the attention of researchers worldwide. The likeness of microorganisms including bacteria, yeast, algae, fungi, and even viruses toward metals is well-known. Higher tolerance to toxic metals has opened up new avenues of designing microbial fabricated nanomaterials. Their synthesis, characterization and applications in bioremediation, biomineralization, and as a chelating agent has been well-documented and reviewed. Further, these materials, due to their ability to get functionalized, can also be used as theranostics i.e., both therapeutic as well as diagnostic agents in a single unit. Current article attempts to focus particularly on the application of such microbially derived nanoformulations as a drug delivery and targeting agent. Besides metal-based nanoparticles, there is enough evidence wherein nanoparticles have been formulated using only the organic component of microorganisms. Enzymes, peptides, polysaccharides, polyhydroxyalkanoate (PHA), poly-(amino acids) are amongst the most used biomolecules for guiding crystal growth and as a capping/reducing agent in the fabrication of nanoparticles. This has promulgated the idea of complete green chemistry biosynthesis of nano-organics that are most sought after in terms of their biocompatibility and bioavailability.
Long-Term Outcomes of Successful Recanalization Compared With Optimal Medical Therapy for Coronary Chronic Total Occlusions in Patients With and Without Left Ventricular Systolic Dysfunction
Authors: Guo Lei , Meng Shaoke , Lv Haichen , Zhong Lei , Wu Jian , Ding Huaiyu , Xu Jiaying , Zhang Xiaoyan , Huang Rongchong
Published: April 2021

Background: The number of coronary chronic total occlusion (CTO) patients with left ventricular (LV) systolic dysfunction is significant, but the clinical outcomes of these patients are rarely reported. The present retrospective cohort study aimed to investigate the long-term outcomes of successful recanalization vs. optimal medical therapy (MT) for CTOs in patients with preserved and impaired LV systolic function.

Methods: A total of 1,895 patients with CTOs were stratified according to LV function. Of these, 1,420 patients (74.9%) with LV ejection fraction (LVEF) >45% and 475 patients (25.1%) with LVEF ≤45% were treated with optimal MT or successful CTO percutaneous coronary intervention (PCI). A 1:1 propensity score matching (PSM) was conducted to reduce the impact of potential confounding on the outcomes. The primary outcome was the frequency of major adverse cardiac events (MACEs).

Results: Throughout a 2.6-year follow-up and after adjusting for confounders, among patients with preserved LV function, successful CTO PCI was associated with reduced incidence of MACE (14.2 vs. 23.9%, adjusted HR 0.63, 95% CI 0.48–0.83, p = 0.001) compared to MT. There was no significant difference in MACE occurrence (29.6 vs. 28.9%, adjusted HR 1.05, 95% CI: 0.71–1.56, p = 0.792) between successful recanalization and MT in patients with LV systolic dysfunction. The primary outcome among patients with impaired and preserved LV systolic function after PSM was similar to that from earlier findings before PSM was conducted. A significant interaction between LV function and therapeutic strategy for MACE was observed (interaction p = 0.038).

Conclusions: Compared to MT alone for management of patients with CTOs, successful CTO PCI may reduce the risk of MACE in patients with preserved LV systolic function, but not in patients with LV dysfunction.
Recruiting and Preparing Undergraduate Students for a Collegiate Debate: An HBCU Case Study
Authors: Wordlaw LaShawn , Harrell Kevin J. , Romocki LaHoma Smith
Published: April 2021

The benefits of debate as an effective pedagogical tool in higher education are well-published. It fosters students’ development of critical thinking, collaboration, creativity, and communication skills. This paper describes a conceptual model of debate categories: in-class debate, co-curricular debate, and tournament debate. It proposes six levels of debate for faculty to employ to create engaged active learning experiences. It is a case study written from the perspective of faculty who served as debate coaches over a four-year period. It shares lessons learned and best practices for recruiting and preparing undergraduate students for a co-curricular debate competition, a subject that is missing in the literature.
Coordinated Cyber-Attack Detection Model of Cyber-Physical Power System Based on the Operating State Data Link
Authors: Wang Lei , Xu Pengcheng , Qu Zhaoyang , Bo Xiaoyong , Dong Yunchang , Zhang Zhenming , Li Yang
Published: April 2021

Existing coordinated cyber-attack detection methods have low detection accuracy and efficiency and poor generalization ability due to difficulties dealing with unbalanced attack data samples, high data dimensionality, and noisy data sets. This paper proposes a model for cyber and physical data fusion using a data link for detecting attacks on a Cyber–Physical Power System (CPPS). The two-step principal component analysis (PCA) is used for classifying the system’s operating status. An adaptive synthetic sampling algorithm is used to reduce the imbalance in the categories’ samples. The loss function is improved according to the feature intensity difference of the attack event, and an integrated classifier is established using a classification algorithm based on the cost-sensitive gradient boosting decision tree (CS-GBDT). The simulation results show that the proposed method provides higher accuracy, recall, and F-Score than comparable algorithms.
The Links of Ghrelin to Incretins, Insulin, Glucagon, and Leptin After Bariatric Surgery
Authors: Skuratovskaia Daria , Vulf Maria , Chasovskikh Nataliya , Komar Aleksandra , Kirienkova Elena , Shunkin Egor , Zatolokin Pavel , Litvinova Larisa
Published: April 2021

Type 2 diabetes mellitus (T2DM) is one of the most prominent and socially significant problems. The present study aimed to identify the mechanisms of interaction of critical regulators of carbohydrate metabolism using bioinformatics and experimental methods and to assess their influence on the development of T2DM. We conducted an in silico search for the relationship of hormones and adipokines and performed functional annotation of the receptors for ghrelin and incretins. Hormones and adipokines were assessed in the plasma of obese patients with and without T2DM as well as after laparoscopic sleeve gastrectomy (LSG) and Roux-en-Y gastric bypass (RYGB) surgeries. Incretin- and ghrelin-associated functions and metabolic processes were discovered. Low ghrelin levels were observed in obese patients without T2DM compared with healthy volunteers and the other groups. The highest ghrelin levels were observed in obese patients with T2DM. This defense mechanism against insulin resistance could be realized through the receptors G-protein-coupled receptor (GPCR), growth hormone secretagogue receptor (GHSR), and growth hormone-releasing hormone receptor (GHRHR). These receptors are associated with proliferative, inflammatory, and neurohumoral signaling pathways and regulate responses to nutrient intake. Signaling through the GPCR class unites ghrelin, glucagon, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide (GLP)-1. Ghrelin impairs carbohydrate and lipid metabolism in obese patients. Ghrelin is associated with elevated plasma levels of insulin, glucagon, and leptin. Specific activation of receptors and modulation by posttranslational modifications of ghrelin can control IR’s development in obesity, which is a promising area for research.
Advances in Genome Editing and Application to the Generation of Genetically Modified Rat Models
Authors: Chenouard Vanessa , Remy Séverine , Tesson Laurent , Ménoret Séverine , Ouisse Laure-Hélène , Cherifi Yacine , Anegon Ignacio
Published: April 2021

The rat has been extensively used as a small animal model. Many genetically engineered rat models have emerged in the last two decades, and the advent of gene-specific nucleases has accelerated their generation in recent years. This review covers the techniques and advances used to generate genetically engineered rat lines and their application to the development of rat models more broadly, such as conditional knockouts and reporter gene strains. In addition, genome-editing techniques that remain to be explored in the rat are discussed. The review also focuses more particularly on two areas in which extensive work has been done: human genetic diseases and immune system analysis. Models are thoroughly described in these two areas and highlight the competitive advantages of rat models over available corresponding mouse versions. The objective of this review is to provide a comprehensive description of the advantages and potential of rat models for addressing specific scientific questions and to characterize the best genome-engineering tools for developing new projects.
Amino Acid Reduction Can Help to Improve the Identification of Antimicrobial Peptides and Their Functional Activities
Authors: Dong Gai-Fang , Zheng Lei , Huang Sheng-Hui , Gao Jing , Zuo Yong-Chun
Published: April 2021

Antimicrobial peptides (AMPs) are considered as potential substitutes of antibiotics in the field of new anti-infective drug design. There have been several machine learning algorithms and web servers in identifying AMPs and their functional activities. However, there is still room for improvement in prediction algorithms and feature extraction methods. The reduced amino acid (RAA) alphabet effectively solved the problems of simplifying protein complexity and recognizing the structure conservative region. This article goes into details about evaluating the performances of more than 5,000 amino acid reduced descriptors generated from 74 types of amino acid reduced alphabet in the first stage and the second stage to construct an excellent two-stage classifier, Identification of Antimicrobial Peptides by Reduced Amino Acid Cluster (iAMP-RAAC), for identifying AMPs and their functional activities, respectively. The results show that the first stage AMP classifier is able to achieve the accuracy of 97.21 and 97.11% for the training data set and independent test dataset. In the second stage, our classifier still shows good performance. At least three of the four metrics, sensitivity (SN), specificity (SP), accuracy (ACC), and Matthews correlation coefficient (MCC), exceed the calculation results in the literature. Further, the ANOVA with incremental feature selection (IFS) is used for feature selection to further improve prediction performance. The prediction performance is further improved after the feature selection of each stage. At last, a user-friendly web server, iAMP-RAAC, is established at http://bioinfor.imu.edu.cn/iampraac.
Rv0954 Is a Member of the Mycobacterial Cell Division Complex
Authors: Wang Ruojun , Ehrt Sabine
Published: April 2021

Proper control of cell division in the intracellular pathogen Mycobacterium tuberculosis is central to its growth, survival, pathogenesis, and resistance to antibiotics. Nevertheless, the divisome components and mechanisms by which mycobacteria regulate their cell cycle are not entirely understood. Here we demonstrate that the previously uncharacterized Rv0954 protein localizes to the mid-cell during cell division and interacts with the division-related proteins LamA, PbpA, and PknH. Deletion of rv0954 did not result in alterations in cell morphology or sensitivity to cell wall-targeting antibiotics but transposon mutagenesis demonstrated genetic interactions with genes related to cell division. This work suggests that Rv0954 participates in cell division and reveals potential components of the mycobacterial divisome for future investigation.
Human Fecal Pollution Monitoring and Microbial Risk Assessment for Water Reuse Potential in a Coastal Industrial–Residential Mixed-Use Watershed
Authors: Kongprajug Akechai , Denpetkul Thammanitchpol , Chyerochana Natcha , Mongkolsuk Skorn , Sirikanchana Kwanrawee
Published: April 2021

Rapid economic development has caused industrial expansion into residential communities, leading to higher fecal pollution loads that could be discharged into aquatic environments. However, little is known regarding the potential microbial impact on human health. This study investigated microbial contamination from coastal industrial–residential community areas in nine sampling sites in waterways during three dry events. A general microbial source tracking (MST) marker, GenBac3, was detected in all samples from all three events, indicating continuing fecal pollution in the area, mostly from human sewage contamination. This was shown by the human-specific genetic marker crAssphage (88.9%) and human polyomavirus (HPyVs; 92.6%) detection. Enteric human adenovirus (HAdV40/41) showed three positive results only from residential sites in the first event. No spatial difference was observed for MST markers and traditional fecal indicators (total coliforms and Escherichia coli) in each event. Still, a significantly lower abundance of GenBac3, HPyVs, and total coliforms in the first sampling event was detected. Spearman’s rho analysis indicated a strong correlation among certain pairs of microbial parameters. Multivariate analysis revealed two clusters of samples separated by land use type (industrial vs. residential). According to factor analysis of mixed data, the land use parameter was more associated with physicochemical parameters (i.e., salinity, conductivity, water temperature, and dissolved oxygen). A Quantitative Microbial Risk Assessment (QMRA) was then conducted to estimate the annual infection risks of HAdV40/41 for non-potable water reuse purposes using predicted concentrations from crAssphage and HPyVs. The highest risks (95th percentiles) were ranked by food crop irrigation, aquaculture, and toilet flushing, at 10–1, 10–2, and 10–3 per person per year (pppy). Required treatment levels to achieve a 10–4 pppy annual infection risk were estimated. QMRA-based water treatment scenarios were suggested, including chlorination for toilet flushing reuse and depth filtration prior to chlorination for aquaculture and food crop irrigation. Microbial monitoring combined with a QMRA could provide better insights into fecal pollution patterns and the associated risks, facilitating effective water quality management and appropriate prior treatments for water reuse.
Co-registration Analysis of Fluorodopa and Fluorodeoxyglucose Positron Emission Tomography for Differentiating Multiple System Atrophy Parkinsonism Type From Parkinson's Disease
Authors: Xian Wen-biao , Shi Xin-chong , Luo Gan-hua , Yi Chang , Zhang Xiang-song , Pei Zhong
Published: April 2021

It is difficult to differentiate between Parkinson's disease and multiple system atrophy parkinsonian subtype (MSA-P) because of the overlap of their signs and symptoms. Enormous efforts have been made to develop positron emission tomography (PET) imaging to differentiate these diseases. This study aimed to investigate the co-registration analysis of 18F-fluorodopa and 18F-flurodeoxyglucose PET images to visualize the difference between Parkinson's disease and MSA-P. We enrolled 29 Parkinson's disease patients, 28 MSA-P patients, and 10 healthy controls, who underwent both 18F-fluorodopa and 18F-flurodeoxyglucose PET scans. Patients with Parkinson's disease and MSA-P exhibited reduced bilateral striatal 18F-fluorodopa uptake (p < 0.05, vs. healthy controls). Both regional specific uptake ratio analysis and statistical parametric mapping analysis of 18F-flurodeoxyglucose PET revealed hypometabolism in the bilateral putamen of MSA-P patients and hypermetabolism in the bilateral putamen of Parkinson's disease patients. There was a significant positive correlation between 18F-flurodeoxyglucose uptake and 18F-fluorodopa uptake in the contralateral posterior putamen of MSA-P patients (rs = 0.558, p = 0.002). Both 18F-flurodeoxyglucose and 18F-fluorodopa PET images showed that the striatum was rabbit-shaped in the healthy control group segmentation analysis. A defective rabbit-shaped striatum was observed in the 18F-fluorodopa PET image of patients with Parkinson's disease and MSA-P. In the segmentation analysis of 18F-flurodeoxyglucose PET image, an intact rabbit-shaped striatum was observed in Parkinson's disease patients, whereas a defective rabbit-shaped striatum was observed in MSA-P patients. These findings suggest that there were significant differences in the co-registration analysis of 18F-flurodeoxyglucose and 18F-fluorodopa PET images, which could be used in the individual analysis to differentiate Parkinson's disease from MSA-P.
Neural Systems Under Change of Scale
Authors: Fagerholm Erik D. , Foulkes W. M. C. , Gallero-Salas Yasir , Helmchen Fritjof , Friston Karl J. , Leech Robert , Moran Rosalyn J.
Published: April 2021

We derive a theoretical construct that allows for the characterisation of both scalable and scale free systems within the dynamic causal modelling (DCM) framework. We define a dynamical system to be “scalable” if the same equation of motion continues to apply as the system changes in size. As an example of such a system, we simulate planetary orbits varying in size and show that our proposed methodology can be used to recover Kepler’s third law from the timeseries. In contrast, a “scale free” system is one in which there is no characteristic length scale, meaning that images of such a system are statistically unchanged at different levels of magnification. As an example of such a system, we use calcium imaging collected in murine cortex and show that the dynamical critical exponent, as defined in renormalization group theory, can be estimated in an empirical biological setting. We find that a task-relevant region of the cortex is associated with higher dynamical critical exponents in task vs. spontaneous states and vice versa for a task-irrelevant region.
Case Report: A Well-Hidden Cause for Myelopathy
Authors: Braun Tobias , Schulz Eva , Viard Maxime , AlhajOmar Omar , Struffert Tobias , Gattenloehner Stefan , Yeniguen Mesut , Juenemann Martin
Published: April 2021

Introduction: Sarcoidosis is a rare, systemic inflammatory disease and can involve multiple organs, especially the lungs and lymph nodes. The nervous system is affected in <10 percent of patients, which is called neurosarcoidosis. Neurosarcoidosis can cause a multitude of symptoms and can mimic various diseases. A rare manifestation is bone marrow involvement. We describe a case of spinal cord syndrome due to myelopathy that was caused by sarcoidosis of the bone marrow.

Case Presentation: A male patient presented to our hospital with incomplete spinal cord syndrome. He suffered from numbness of the legs which had progressed to severe paraparesis. Magnetic resonance imaging revealed thoracic myelopathy without contrast enhancement. Thorough diagnostics found no explanation for the myelopathy, and the patient was treated symptomatically with high-dose steroids. When the patient developed non-resolving leukopenia, a bone marrow biopsy was performed. The bone marrow showed changes due to sarcoidosis. Further testing revealed myocardial involvement of the sarcoidosis. The patient was started on oral prednisolone and methotrexate. Over the course of time, his symptoms improved, but he still suffers from spastic leg paresis and needs aids to walk farther than 1 kilometre.

Conclusion: In patients presenting with neurological deficits of unknown cause, neurosarcoidosis is a potential explanation. If it manifests primarily in the bone marrow, the diagnosis can be easily overlooked. Abnormalities in a full blood count should make the treating physician consider this diagnosis, and a bone marrow biopsy should be performed.
FOXO3A Expression in Upper Tract Urothelial Carcinoma
Authors: Zhang Guoyao , Shi Wanping , Jia Enzhao , Zhang Lei , Han Yongsheng , Rodriguez Ronald , Ma Tianjiang
Published: April 2021

Background

Epidemiological studies have reported various results regarding whether FOXO3A is related to various carcinomas. However, the prognostic significance of FOXO3A in upper tract urothelial carcinoma (UTUC) remains unclear. The purpose of this study was to validate the correlation between FOXO3A expression and oncological outcomes in UTUC.

Methods

The expression levels of FOXO3A in 107 UTUC patients were examined by immunohistochemistry (IHC). We examined the prognostic role of FOXO3A by using the Cox proportional hazard model.

Results

The results indicated that FOXO3A expression was notably decreased in UTUC tissue compared with control tissue. Decreased expression of FOXO3A was also related to advanced pathologic stage (P = 0.026), lymph node metastasis (P = 0.040), lymphovascular invasion (P < 0.001), and adjuvant therapy (P = 0.048). In addition, UTUC patients with low FOXO3A expression had a significantly shorter survival time, including both overall survival (OS) [hazard ratio (HR) 2.382, P = 0.004] and recurrence-free survival (RFS) (HR 2.385, P = 0.004), than those with high expression. Multivariate analyses showed that FOXO3A was a significant predictor for OS (HR 2.145, P = 0.014) and RFS (HR 2.227, P = 0.010) in UTUC patients.

Conclusion

Our results indicate that FOXO3A may be involved in the recurrence of UTUC and that it has certain clinical value in the therapeutic targeting and prognostic evaluation of UTUC.
Efficacy of Combination Chemo-Immunotherapy as a First-Line Treatment for Advanced Non-Small-Cell Lung Cancer Patients With HER2 Alterations: A Case Series
Authors: Zhao Shuang , Xian Xinghong , Tian Panwen , Li Weimin , Wang Ke , Li Yalun
Published: April 2021

Objective

Although the treatment of non-small-cell lung cancer (NSCLC) patients with human epidermal growth factor receptor 2 (HER2) alterations has been studied for years, the overall response rate (ORR) of these patients is still unsatisfactory, and more therapeutic strategies are needed. Little is known about the combination of chemo- and immunotherapy in HER2-altered lung cancer treatment.

Materials and Methods

We report five cases of advanced NSCLC with HER2 insertion mutation or amplification treated with immunotherapy combined with chemotherapy as the first-line treatment. The HER2 alteration type, duration of treatment and survival were also analyzed.

Results

The five advanced NSCLC patients, three with HER2 mutations and two with HER2 amplifications, received chemo-immunotherapy as the first-line treatment. The average patient age was 54.6 years. Three patients were females, and two were males. Among all the patients, only one had a smoking history. The immunotherapies used were as follows: two patients were treated with sintilimab, and three patients were treated with pembrolizumab. Only one patient had squamous carcinoma, and she was also the only patient with a complete response (CR). The progression-free survival (PFS) ranged from 2-12 months, with a median PFS of 8.0 months.

Conclusions

Chemo-immunotherapy may be a promising first-line treatment option for NSCLC patients with HER2 alterations. Further clinical trials are required to confirm this therapeutic option.
Neurocognitive and Behavioral Outcomes of Chinese Survivors of Childhood Lymphoblastic Leukemia
Authors: Peng Liwen , Yang Lok Sum , Yam Perri , Lam Chun Sing , Chan Agnes Sui-yin , Li Chi Kong , Cheung Yin Ting
Published: April 2021

Background

Increasing attention has been dedicated to investigate modifiable risk factors of late effects in survivors of childhood cancer. This study aims to evaluate neurocognitive and behavioral functioning in a relatively young cohort of survivors of childhood acute lymphoblastic leukemia (ALL) in Hong Kong, and to identify clinical and socio-environmental factors associated with these outcomes.

Methods

This analysis included 152 survivors of childhood ALL who were ≥5 years post-diagnosis (52% male, mean [SD] age 23.5[7.2] years at evaluation, 17.2[7.6] years post-diagnosis). Survivors completed performance-based neurocognitive tests, and reported their emotional and behavioral symptoms using the Child/Adult Behavior Checklist. Socio-environmental variables (living space, fatigue, physical activity, family functioning, and academic stress) were self-reported using validated questionnaires. Clinical variables and chronic health conditions were extracted from medical charts. Multivariable linear modeling was conducted to test identify factors associated with neurocognitive/behavioral outcomes, adjusting for current age, sex, age at diagnosis and cranial radiation. An exploratory mediation analysis was performed to examine the mediating effects of risk factors on neurocognitive and behavioral outcomes.

Results

As compared to population norms, a minority of survivors developed mild-moderate impairment in motor processing speed (36.2%), memory (9.2%) and attention measures (4.0%-10.5%). Survivors also reported attention problems (12.5%), sluggish cognitive tempo (23.7%) and internalizing (depressive, anxiety and somatic symptoms) problems (17.1%). A minority of survivors developed mild-moderate treatment-related chronic conditions (n=37, 24.3%). As compared to survivors without chronic conditions, survivors with chronic conditions had more executive dysfunction (B=5.09, standard error [SE]=2.05; P=0.014) and reported more attention problems (B=5.73, SE=1.43; P<0.0001). Fatigue and poor family functioning was associated with multiple measures of behavior problems (all P<0.001). A lower level of physical activity was correlated with more self-reported symptoms of inattention (B= -1.12, SE=0.38, P=0.004) and sluggish cognitive tempo (B=-1.22, SE=0.41, P=0.003). Exploratory analysis showed that chronic health conditions were associated with behavioral measures through fatigue as the mediator.

Conclusion

The majority of young Chinese survivors of ALL had normal cognitive and behavioral function. Regular monitoring of behavioral function should be performed on survivors who develop treatment-related chronic conditions. Health behavior and socio-environment factors may be potentially modifiable risk factors associated with health outcomes in survivors.
Shaoyao Decoction Inhibits Inflammation and Improves Intestinal Barrier Function in Mice With Dextran Sulfate Sodium-Induced Colitis
Authors: Chi Honggang , Wang Dan , Chen Mengting , Lin Jiantao , Zhang Shuhua , Yu Fengyan , Zhou Jun , Zheng Xuebao , Zou Ying
Published: April 2021

Shaoyao decoction (SYD), a classical traditional Chinese medicine formula, is effective for the treatment of inflammatory bowel disease (IBD). This study was designed to investigate the therapeutic effects of SYD on IBD and possible mechanisms. Dextran sulfate sodium (DSS, 3.5%) was used to induce colitis in C57BL/6 mice. Disease phenotypes were investigated based on disease activity index (DAI), colon length, and microscopic and macroscopic scores. Additionally, the presence of proinflammatory cytokines, immune cell infiltrates, intestinal cell proliferation, apoptosis, epithelial permeability, signal transducer and activator of transcription 3 (STAT3), and nuclear factor-κB (NF-κB) signaling, as well as the intestinal mucosal barrier function, were investigated. The administration of SYD significantly ameliorated the clinical signs, suppressed the levels of proinflammatory cytokines, and reduced immune cell infiltrates into colonic tissues of DSS-induced colitis model mice. SYD also significantly reduced the DSS-induced activation of STAT3 and NF-κB signaling. Furthermore, SYD promoted epithelial integrity by regulating epithelial cell apoptosis and epithelial permeability. Finally, we demonstrated that SYD protected the intestinal barrier function by significantly regulating the mucus layer genes Muc1, Muc2, Muc4, and Tff3, as well as the epithelial barrier genes Z O -1 and Occludin. Our results indicate that SYD has a protective effect on DSS-induced colitis, which is attributable to its anti-inflammatory activity and intestinal barrier function-enhancing effects. These results provide valuable insights into the pharmacological actions of SYD for the treatment of IBD.
Comparison of Pancreatic Damage in Rats for Two Methods of Paraquat Administration
Authors: Gao Yanxia , Hou Linlin , Wang Yibo , Zhang Yan , Zhang Shoutao , Li Yi , Jiang Yanan , Zhu Changju , Sun Tongwen , Duan Guoyu , Yuan Ding
Published: April 2021

It is noted that elevated serum amylase levels suggesting pancreatic damage has an association with prognosis in PQ patients. This study aimed to determine whether PQ can cause pancreatic damage. The two conventional models (intragastric infusion (iG) and intraperitoneal injection (iP)) may exhibit different effects on the pancreas depending on whether or not they pass through the digestive tract. In this study, the rats were divided into four groups: the intragastric infusion group (PQ-iG, n = 45), intraperitoneal injection group (PQ-iP, n = 53), normal control group 1 (NC-iG, n = 6) and normal control group 2 (NC-iP, n = 6). Pancreatic damage was compared between groups using serum amylase activity assay, hematoxylin and eosin (H&E) staining, TUNEL assay, and transmission electron microscopy (TEM). Serum amylase levels in group PQ-iG were significantly higher than in group PQ-iP (p < 0.05). Examination of the H&E sections showed damage to the pancreas. Both experimental groups were displayed inflammatory infiltration within 9 h of PQ treatment. After 9 h, patchy necrosis was observed in group PQ-iP, when inflammatory infiltration was still the dominant pathology. Necrosis appeared and gradually worsened in group PQ-iG, in which necrosis was the dominant pathology. The TUNEL assay showed significantly higher numbers of apoptotic cells in the pancreas of PQ-groups than in the control NC- groups (p < 0.05). TEM showed expansive endoplasmic reticulum lumens and mitochondria swelling in the pancreas of the PQ-groups. It is concluded that both methods of modeling could cause pancreatic damage and the type and degree of damage would change over time. Note that pancreatic damage in group PQ-iG was more severe than that in group PQ-iP. Therefore, clinical practitioners should pay close attention to pancreatic damage caused by PQ, especially when the route of PQ administration was oral.