bluuebunny/crossref_metadata_2025 huggingface dataset:
Drenos torácicos mal posicionados diagnosticados por exame de imagem
Authors: Pantoja Gessica Kelem Carvalho , Saraiva Katleem de Sousa , Castro Neto Renor Gonçalves de , Silva Ádria Rodrigues da , Franco Ana Paula Mota
Published: April 2021

A drenagem torácica é um método que através no qual através de um dreno é retirado substâncias seja ela sanguinolentas como em um hemotórax, ou o ar, no caso do pneumotórax, para que assim seja possível o deslizamento entre as pleuras e mantenha uma adequada expansão pulmonar. No caso de pacientes em que tiveram má inserção do dreno na cavidade pleural pode haver uma piora do quadro clínico, com uma redução da ventilação, insuficiência respiratória, ocorrência de infeções, ou mesmo o pneumotórax iatrogênico. Objetivo: Analisar os achados de imagem de drenos de tórax mal posicionados na tomografia computadorizada. Materiais e métodos: Esta pesquisa trata-se de um estudo retrospectivo, quantitativo com enfoque descritivo, no qual foi utilizado dados de exames de tomografia computadorizadas disponibilizados pela clínica Polimagem Radiodiagnóstico no município de Marabá-PA. Resultados: No presente estudo o grupo que tem maior incidência de complicações relacionadas ao posicionamento inadequado do dreno foi do sexo masculino, entre 19 a 59 anos, indicado por causas traumáticas, o local mais comum de inserção do dreno incorreto ocorreu na região intraparenquimatosa causando como principais complicações o pneumotórax, sangramentos e nos casos mais avançados o surgimento de fistulas. Conclusão: Os achados do exame de imagem tiveram essencial importância para detectar a iatrogenia causada pelos drenos mal inseridos, os resultados devem ser ampliado para evitar a inadequada colocação de dreno, adotando também protocolos hospitalares padronizados e treinamento da equipe de saúde para sua utilização.
Atividades farmacológicas e sua relação com o estresse oxidativo de Morinda citrifolia L. (Rubiaceae): uma revisão integrativa
Authors: Gomes-Sousa Nathália Cássia , Nunes Lucas dos Santos , Martins Hanna Patrícia dos Santos , Percário Sandro , Dolabela Maria Fâni
Published: April 2021

O presente trabalho fez uma análise de estudos farmacológicos de Morinda citrifolia L. e o papel do estresse oxidativo. A pesquisa foi realizada no Portal de Periódicos da Capes e PubMed. Inicialmente, foram lidos os títulos, resumos e excluídos os que não tinham relação com o tema e em duplicidade. Após esse processo, os trabalhos foram lidos na íntegra e realizada a extração das informações. Foram encontrados no total 517 artigos, após a leitura dos títulos e resumos, foram selecionados 39 artigos e ao final incluídos 28. Em relação às atividades avaliadas, 9 artigos avaliaram a atividade antioxidante e anti-inflamatória; 5 antitumoral e citotoxicidade; 3 antimicrobianos; 3 antileishmania; e 8 artigos que pesquisaram sobre diferentes atividades. De acordo com os estudos analisados esta espécie possui potencial anti-inflamatório, hipotensor, prevenção de pancreatite, hepatoprotetor e citoprotetor, e tais atividades parecem estar relacionadas a presença de metabólitos com atividade antioxidantes. A atividade antitumoral pode estar relacionada à atividade oxidante das antraquinonas. A participação do estresse oxidativo no efeito hipoglicemiante e antiobesidade da espécie ainda precisa ser melhor investigada. Em síntese, a maioria das atividades biológicas atribuídas a M. citrifolia pode ser relacionada a presença de compostos com potencial antioxidante.
Delineamento dos casos de lesão renal de um hospital privado do interior de São Paulo
Authors: Costa Mariana Paula Rodrigues , Ravagnani Juliana Furlan , Rodrigues Aline Scharr , Milagres Clarice Santana
Published: April 2021

A Doença Renal Crônica é caracterizada como uma Doença Crônica Não Transmissível que atinge proporções mundiais. Fatores que contribuem para o avanço desse quadro, é o aumento da incidência das doenças de base como Hipertensão Arterial Sistêmica (HAS) e Diabetes mellitus (DM) e a elevada ocorrência de Injúria Renal Aguda em ambientes intra-hospitalares. Objetivo: identificar o quadro dos pacientes com lesão renal que realizaram tratamento hemodialítico em um hospital privado do interior de São Paulo. Métodos: estudo transversal, retrospectivo, descritivo, com abordagem quantitativa, realizado através da análise de prontuários eletrônicos de um hospital particular, entre os meses de janeiro a junho de 2017. Realizou-se análise estatística exploratória, com análise de frequência dos dados obtidos. Resultados: foram analisados 58 prontuários. A média da idade identificada foi 70,7 anos (±15,5), com mínima de 28 anos e máxima de 98 anos. Quanto às condições de saúde, 63,7% apresentavam história pregressa de Hipertensão Arterial Sistêmica, enquanto metade da amostra apresentava cardiopatias e o Diabetes mellitus foi constatado em 41,3% da amostra. O diagnóstico inicial relacionado às doenças cardiovasculares correspondeu a 32,7% dos dados, sepses a 20,6% e as insuficiências renais estiveram presentes em 8,6% destes diagnósticos. Em relação à Terapia Renal Substitutiva, aproximadamente 80% possuíam Doença Renal Aguda, predominando o acesso vascular temporário de triplo lúmen. Conclusão: identificar os fatores que contribuem com o quadro de DRC intra-hospitalar oportuniza melhor condição de salvaguardar a vida dos pacientes, assim como possibilita a identificação precoce de fatores de risco de piora da função renal.
Impaired larval development at low salinities could limit the spread of the non-native crab Hemigrapsus takanoi in the Baltic Sea
Authors: Nour OM , Pansch C , Lenz M , Wahl M , Clemmesen C , Stumpp M
Published: April 2021

The Asian shore crab Hemigrapsus takanoi, native to the northwest Pacific Ocean, was recently discovered in Kiel Fjord (southwestern Baltic Sea). In laboratory experiments, we tested the salinity tolerance of H. takanoi across 8 levels (0 to 35) and across 3 life history stages (larvae, juveniles and adults) to assess its potential to invade the brackish Baltic Sea. Larval development at different salinities was monitored from hatching to the megalopa stage, while survival and feeding of juveniles and adults were assessed over 17 d. Larvae of H. takanoi were able to complete their development to megalopa at salinities ≥ 20 and the time needed after hatch to reach this stage did not differ between salinities of 20, 25, 30 and 35. At a salinity of 15, larvae still reached the last zoea stage (zoea V), but development to the megalopa stage was not completed. All juveniles and adults survived at salinities from 5 to 35. Feeding rates of juveniles increased with increasing salinity across the entire salinity range. However, feeding rates of adults reached their maximum between salinities of 15 and 35. Our results indicate that both juveniles and adults of H. takanoi are euryhaline and can tolerate a wide range of salinities, at least for the time period tested (2 wk). However, larval development was impaired at salinities lower than 20, which may prevent the spread of H. takanoi into the Baltic Proper.
Demographic consequences of harvesting: a case study from a small and isolated moose population
Authors: Herfindal I , Lee AM , Hamel S , Solberg EJ , Sæther BE
Published: April 2021

Harvesting can have a substantial impact on population dynamics and individual performance in wild populations. While the direct consequences of harvest on individual survival and population growth rate are often apparent, harvesting can also have indirect and more subtle demographic consequences. Disentangling these consequences, however, requires in-depth knowledge of individual life histories of both females and males in the population. Here, we summarise demographic research on a population where such data exist: the Vega moose population in northern Norway. In this population, vital rates vary considerably among both females and males, and harvesting increases this variation by generating positive covariation between reproductive performance and survival. The skewed age and sex structure, which is typical of many harvested populations, also has demographic consequences: it reduces the ratio of effective to total population size and influences variation in vital rates in males and females. The moose harvest at Vega is structured by age- and sex-specific quotas, but it is not intentionally selective regarding size or other phenotypic characteristics. Still, harvest selection for earlier birth rates and larger calves was apparent, likely due to habitat-performance relationships and habitat-specific harvest mortality. Together, the bulk of research on this population shows that harvesting impacts population demography through many different pathways, with some being more subtle than others. These complex pathways influence the demographic variance and affect stochastic processes such as population growth, genetic drift, and rates of evolutionary change, and they must therefore be acknowledged in management plans to achieve sustainable harvesting.
Sistem Kontrol Pelanggaran Merokok Santri Di Ppnj Menggunakan Mikrokontroller Dan Internet Of Thing (Iot)
Authors: Prastiono Edy , Tijaniyah Tijaniyah
Published: April 2021

Pondok Pesantren Nurul Jadid (PPNJ) merupakan sebuah lembaga pendidikan pondok pesantren yang berlokasi di Desa Karang Anyar Kecamatan Paiton Kabupaten Probolinggo. Pondok Pesantren Nurul Jadid dapat menghasilkan lulusan yang berkualitas baik secara intelektual. Seorang santri dapat mempelajari ilmu agama maupun ilmu pendidikan lainnya bertujuan untuk mengajarkan santri tersebut kedisiplinan. Santri diwajibkan mentaati peraturan yang ditetapkan didalam pesantren tersebut. Salah satunya peraturan dilarang merokok (bagi santri putra) karena asap rokok sangat berbahaya bagi kesehatan. Apabila ada santri yang melanggar akan dikenakan sanksi sesuai dengan pelangaran yang dilakukan. Selama ini pelanggaran merokok jarang diketahui oleh pengurus pesantren sehingga santri tidak dikenakan sanksi atas pelanggaran yang dibuat karena ketidak tahuan pengurus pesantren. Untuk mengatasi masalah di atas, maka dibuatlah alat yang mampu membantu para pengurus pesantren dengan memanfaatkan teknologi Internet of Things (IOT).Alat ini dirancang dapat membantu pengurus agar dapat menindak lanjuti santri yang melanggar, pengurus hanya mendapatkan pesan telegram. Alat ini menggunakan nodemcu esp8266 sebagai mikrokontroler yang dilengkapi dengan modul wifi. Dan sensor mq2 untuk mendeteksi asap rokok di kamar santri putra. Jika sensor mendeteksi asap rokok maka nodemcu esp 8266 akan mengirim pesan ke telegram. Jika sensor mq 2 tidak mendeteksi asap rokok maka nodemcu esp 8266 tidak mengirim pesan telegram.
Audit Energi Dan Analisa Peluang Penghematan Konsumsi Energi Pada Sistem Air Conditioning Di Ruangan Laboratorium Fakultas Teknik Universitas Nurul Jadid
Authors: Sayuti Muhammad , Herlina Amalia
Published: April 2021

Air Conditioning merupakan suatu peralatan yang digunakan untuk mengkondisikan udara sehingga dapat mencapai temperatur dan kelembaban yang sesuai dengan kondisi udaranyaman sesuai Standar Nasional Indonesia (SNI) 03-6572-2001. Audit energi adalah kegiatanuntuk mengidentifikasi seberapa banyak energi yang digunakan serta langkah-langkah yang diperlukan untuk menghemat energi pada fasilitas energi tersebut. Energi listrik digunakan untuk menyalakan alat-alat elektronik salah satunya Air Conditioning. Ada beberapa ruangan yang menggunakan Air Conditioning di Fakultas Teknik Universitas Nurul Jadid salah satunya yaitu di Ruangan Laboratorium yang paling banyak penggunaan konsumsinya. Penelitian ini bertujuan untuk mengetahui penggunaan energi listrik dengan menghitung intensitas konsumsi energi (IKE), mencari kebutuhan air conditioning disetiap ruangannya dengan menghitung british thermal unit (BTU) dan besar estimasi kebutuhan Air Conditioning terhadap masing-masing ruangannya serta menganalisa peluang penghematan konsumsi energi pada Air Conditioning di Laboratorium Fakultas Teknik Universitas Nurul Jadid.  Berdasarkan hasil pengukuran intensitas konsumsi energi (IKE) awal menunjukkan bahwa penggunaan energi listrik di Ruangan Laboratorium Fakultas Teknik Universitas Nurul Jadid adalah 99,034 kWh/bulan dengan setting ac remote ruangan 16°C terdapat suhu ruangan 24°C selama 6 Jam, Kemudian setelah menganalisa peluang penghematannya terdapat nilai 64,86 kWh/bulan dengan setting ac remote 16°C untuk mencapai suhu ruangan 22°C selama 4 jam. Hasil perhitungan british thermal unit (BTU) menunjukkan kebutuhan Air Conditioning menurut ruangannya sudah memenuhi standarisasi pemakaiannya, tetapi kurang stabil. Kemudian peluang penghematannya untuk melakukan penyeimbangan beban, mengurangi jam operasinya, matikan Air Conditioning apabila sudah digunakan.
Samuel Beckett and Disability Performance
Authors: Simpson Hannah
Published: April 2021

Beckett's plays have attracted a striking range of disability performances, in part because of their insistent attention on embodied existence and the impaired body. Here, I examine four recent disability performances of Beckett's plays, exploring how these productions prompt re-evaluation of the previously undetected indicators of disability in the scripts, including mobility impairment, automatic speech, stuttering, and memory deficiency. Drawing on a series of original interviews with the practitioners in question, I examine the intersection between textual aesthetics and disability ethics in these contemporary productions, emphasising how these performances illuminate crucial corporeal, social, and ontological concerns in Beckett's original scripts, in newly embodied terms.
Cardiac complications in patients with severe COVID-19 pneumonia
Authors: Yaroshchuk N. А. , Kochmasheva V. V. , Vakhrameev A. V.
Published: April 2021

This article is devoted to the analysis of the most frequent cardiac complications in patients with severe community-acquired pneumonia caused by COVID-19 viral infection. The study found that cardiac complications developed in 25% of patients with COVID-19 pneumonia. The most common complication was supraventricular rhythm disturbances. Atrial fibrillation and flutter proceeded with pronounced hemodynamic changes. Myocardial injury, given the increase in cardiospecific troponin T, could be suspected in 38% of patients. Differential diagnosis between ACS and myocarditis caused the greatest difficulties.
Cuando la emergencia se vuelve parte de la vida cotidiana: revisión de un concepto central de la educación en emergencias en el contexto de la guerra contra las drogas
Authors: Shirazi Roozbeh
Published: April 2021

Si bien "emergencia" es un concepto clave en el campo de la educación en emergencias (EeE), los académicos y especialistas han sido ambivalentes con respecto a este término y las condiciones a las que se refiere. A partir del trabajo de la antropóloga Janet Roitman, en este artículo propongo revisar de forma crítica los conceptos de emergencia y crisis. Asimismo, propongo que entender "emergencia" como si fuese un momento de conmoción o un hecho inesperado oscurece la forma en la que condiciones aparentemente normales pueden producir sus propios impases. En lugar de caracterizarse por un consenso de significado, las crisis implican construcciones narrativas que crean nuevas temporalidades, al mismo tiempo que enmarcan solo ciertas preguntas y respuestas como posibles. En este artículo yuxtapongo dos construcciones narrativas de crisis en la cultura popular para explorar cómo las construcciones narrativas sobre la guerra contra las drogas pueden producir dos relatos discordantes y diferentes sobre las crisis que dicen representar. Sugiero que prestar atención de manera explícita a las políticas que subyacen a la narración de la crisis, incluso si este ejercicio complica el diseño de la respuesta a la emergencia, es vital para nombrar y resolver posibles puntos ciegos éticos e impases en el campo de la EeE.
THE RESULTS OF EUROPEAN ELECTIONS 2019: NEW ALIGNMENT OF FORCES IN THE EUROPEAN PARLIAMENT AND EUROPEAN COMMISSION, INCLUDING GENDER ASPECT
Authors:   The Institute of Europe RAS, Moscow, Russian Federation, GUSELETOV BORIS
Published: April 2021

The article presents an analysis of the results of the 2019 elections of members of the European Parliament and the formation of a new composition of the European Commission. The question of how the balance of power has changed in the new Parliament between the traditionally leading parties of the European conservatives (European people's party) and socialists (Party of European socialists), on the one hand, and the other parties (Liberals, Greens, Communists, etc.), which traditionally play a secondary role, on the other. The results of the so-called eurosceptic parties, which in recent years have significantly increased their influence both at the European and national levels, are analyzed. It shows how the election results affected the distribution of leadership positions in the European Parliament itself, as well as their impact on the formation of the new composition of the European Commission. The article examines how the mechanism of interaction between the European Parliament and the European Council has changed during the formation of the European Commission and what impact these changes have on the prospects for future interaction between these institutions. In conclusion, the prospects for further development of the European Union are outlined, including the need to reform its political and socio-economic systems.
DOVEVA MORIRE? L'ATTENTATO DI ZANIBONI A MUSSOLINI: FRA VERITà E MENZOGNE
Authors:   Università di Trieste, Trieste, Italia, PIETRO NEGLIE
Published: April 2021

The purpose of this work is to demonstrate the political weakness of the socialist party in the face of fascism, its compliance and inability to organize a real opposition, left to individual initiative, easy to control and exploit. To this end, we focus on Zaniboni's attack on Mussolini, an isolated and desperate gesture that highlighted the lack of a true opposition policy. The present essay then analyzes both the pacification pact of 1921 signed by fascists and socialists and the genesis of the attack and its organization are analyzed. This attack was the first of four, all in 1926. From the beginning it appeared so anomalous that the international press spoke of a farce; in fact it was soon learned that the security services knew everything, indeed they had partly facilitated it. Mussolini was very skilled in managing the attack, useful both to demonstrate the need for restrictive measures, and to demonstrate the political irrelevance of the opposition, which even reached terrorism: the same night the unitary socialist party and the invisible Masonic Lodges were dissolved. to Mussolini. In the conclusions, thanks to the documents recovered in the state archive, the figure of the bomber is resized: not a man who lives his detention with pride, without the shadow of a doubt or an afterthought, but a man left alone, grateful to the Duce for the financial help given to his daughter, to make her follow her studies. For this reason he said he was ready to “make himself available”.
3D Cancer Models: The Need for a Complex Stroma, Compartmentalization and Stiffness
Authors: Pape Judith , Emberton Mark , Cheema Umber
Published: April 2021

The use of tissue-engineered 3D models of cancer has grown in popularity with recent advances in the field of cancer research. 3D models are inherently more biomimetic compared to 2D cell monolayers cultured on tissue-culture plastic. Nevertheless 3D models still lack the cellular and matrix complexity of native tissues. This review explores different 3D models currently used, outlining their benefits and limitations. Specifically, this review focuses on stiffness and collagen density, compartmentalization, tumor-stroma cell population and extracellular matrix composition. Furthermore, this review explores the methods utilized in different models to directly measure cancer invasion and growth. Of the models evaluated, with PDX and in vivo as a relative “gold standard”, tumoroids were deemed as comparable 3D cancer models with a high degree of biomimicry, in terms of stiffness, collagen density and the ability to compartmentalize the tumor and stroma. Future 3D models for different cancer types are proposed in order to improve the biomimicry of cancer models used for studying disease progression.
Quantifying the Resilience of the U.S. Domestic Aviation Network During the COVID-19 Pandemic
Authors: Bauranov Aleksandar , Parks Steven , Jiang Xuan , Rakas Jasenka , González Marta C.
Published: April 2021

This paper analyzes the impacts of COVID-19 pandemic on the United States air transportation network between March and August 2020. Despite dramatic reductions in flight and passenger volumes, the network remained robust and resilient against perturbation. Although 24% of airports closed, the reduction in network efficiency was only 5.1%, which means airlines continued to serve most destinations. A deeper analysis of airport closures reveals that 1) small peripheral airports were the most likely to be closed; 2) socio-economic and epidemiological factors characterizing the airport’s region such as income, income inequality, political leaning, and the number of observed COVID cases were not predictive of airport closure. Finally, we show that high network robustness has a downside: although emissions from United States air traffic in 2020 fell by 37.4% compared to 2019, mostly due to the drop in the number of flights, emissions per passenger doubled in the period April to August 2020 and increased eightfold in the week of April 5–11. This rise indicates inefficient use of resources by airlines.
Interaction Phenomena to Be Accounted for Human-Induced Vibration Control of Lightweight Structures
Authors: Díaz Iván M. , Gallegos Christian A. , Ramírez Senent José , Renedo Carlos M. C.
Published: April 2021

Inertial mass controllers, including passive, semi-active and active strategies, have been extensively used for canceling human-induced vibrations in lightweight pedestrian structures. Codes to check the vibration serviceability and current controller design approaches assume that both excitation forces and controller forces are the same on a flexible structure and on a rigid structure. However, this fact may not be assumable since interaction phenomena arise even for moderately lightweight structures. Analyzing two case studies in this paper, interaction phenomena involved in the frequency-domain-based design of passive and active inertial mass dampers are discussed. Thus, a general vibration control problem including the interaction phenomena is set hereby. Concretely, this paper deeply discusses the following issues: (i) how the structure to be controlled is affected when human-structure interaction is presented for deterministic and stochastic conditions, (ii) the closed-loop transfer function of the controlled structure including a passive inertial mass damper, and (iii) the closed-loop transfer function of the controlled structure including an active inertial mass damper. In addition, the performed analysis considers the actuator dynamics and the actuator-structure interaction.
Polydatin Inhibits Cell Viability, Migration, and Invasion Through Suppressing the c-Myc Expression in Human Cervical Cancer
Authors: Bai Longchang , Ma Yingkang , Wang Xue , Feng Qiongni , Zhang Zhining , Wang Sijie , Zhang Huijie , Lu Xinyu , Xu Yonghui , Zhao Erhu , Cui Hongjuan
Published: April 2021

Polydatin, an active ingredient from the roots of Polygonum cuspidatum, is considered to have protective effects on the cardiovascular system and liver. In this study, we demonstrated that polydatin has antitumor activity against human cervical cancer. Polydatin efficiently inhibited cervical cancer cell proliferation by regulating cell cycle-related proteins including p21, p27, CDK2, CDK4, Cyclin D1, and Cyclin E1. Furthermore, polydatin suppressed cell invasion and migration by regulating epithelial–mesenchymal transition (EMT) markers, including E-cadherin, N-cadherin, Snail and Slug. The c-Myc, as a proto-oncogene, is considered to be closely associated with the proliferation and metastasis of tumor cells. After polydatin treatment, the protein expression of c-Myc showed a significant decrease. Based on these data, we overexpressed c-Myc in cervical cancer cells and observed that the overexpression of c-Myc rescued the inhibitory effect of polydatin on cell proliferation and metastasis. These results indicated that polydatin can inhibit cell proliferation and metastasis through suppressing the c-Myc expression in human cervical cancer.
Crtc1 Deficiency Causes Obesity Potentially via Regulating PPARγ Pathway in White Adipose
Authors: Hu Yimeng , Lv Jian , Fang Yu , Luo Qiang , He Yuan , Li Lili , Fan Mingxia , Wang Zhihua
Published: April 2021

Obesity is characterized by excessive fat accumulation and associated with glucose and lipid metabolism disorders. Crtc1, a transcription cofactor regulating CREB activity, has been involved in the pathogenesis of metabolic syndrome; however, the underlying mechanism remains under debate. Here we generated a Crtc1–/– mouse line using the CRISPR/Cas9 system. Under normal feeding conditions, Crtc1–/– mice exhibited an obese phenotype resultant from the abnormal expansion of the white adipocytes. The development of obesity in Crtc1–/– mice is independent of alterations in food intake or energy expenditure. Moreover, Crtc1–/– mice were more prone to insulin resistance and dyslipidemia, as evidenced by higher levels of plasma glucose, insulin and FABP4 than wildtype mice. Transcriptome analysis in liver and epididymal white adipose tissue (eWAT) showed that the fat accumulation caused by Crtc1 deletion was mainly related to lipid metabolism in adipose tissue, but not in liver. GSEA and KEGG analysis identified PPAR pathway to be of the highest impact on lipid metabolism in eWAT. This regulation was independent of a direct interaction between CRTC1 and PPARγ. Our findings demonstrate a crucial role of Crtc1 in regulating lipid metabolism in adipose during development, and provide novel insights into obesity prevention and therapeutics.
Different Forms of Tumor Vascularization and Their Clinical Implications Focusing on Vessel Co-option in Colorectal Cancer Liver Metastases
Authors: Haas Gwendolyn , Fan Shuang , Ghadimi Michael , De Oliveira Tiago , Conradi Lena-Christin
Published: April 2021

In modern anti-cancer therapy of metastatic colorectal cancer (mCRC) the anti-angiogenic treatment targeting sprouting angiogenesis is firmly established for more than a decade. However, its clinical benefits still remain limited. As liver metastases (LM) represent the most common metastatic site of colorectal cancer and affect approximately one-quarter of the patients diagnosed with this malignancy, its treatment is an essential aspect for patients' prognosis. Especially in the perioperative setting, the application of anti-angiogenic drugs represents a therapeutic option that may be used in case of high-risk or borderline resectable colorectal cancer liver metastases (CRCLM) in order to achieve secondary resectability. Regarding CRCLM, one reason for the limitations of anti-angiogenic treatment may be represented by vessel co-option (VCO), which is an alternative mechanism of blood supply that differs fundamentally from the well-known sprouting angiogenesis and occurs in a significant fraction of CRCLM. In this scenario, tumor cells hijack pre-existing mature vessels of the host organ independently from stimulating new vessels formation. This represents an escape mechanism from common anti-angiogenic anti-cancer treatments, as they primarily target the main trigger of sprouting angiogenesis, the vascular endothelial growth factor A. Moreover, the mechanism of blood supply in CRCLM can be deduced from their phenotypic histopathological growth pattern (HGP). For that, a specific guideline has already been implemented. These HGP vary not only regarding their blood supply, but also concerning their tumor microenvironment (TME), as notable differences in immune cell infiltration and desmoplastic reaction surrounding the CRCLM can be observed. The latter actually serves as one of the central criteria for the classification of the HGP. Regarding the clinically relevant effects of the HGP, it is still a topic of research whether the VCO-subgroup of CRCLM results in an impaired treatment response to anti-angiogenic treatment when compared to an angiogenic subgroup. However, it is well-proved, that VCO in CRCLM generally relates to an inferior survival compared to the angiogenic subgroup. Altogether the different types of blood supply result in a relevant influence on the patients' prognosis. This reinforces the need of an extended understanding of the underlying mechanisms of VCO in CRCLM with the aim to generate more comprehensive approaches which can target tumor vessels alternatively or even other components of the TME. This review aims to augment the current state of knowledge on VCO in CRCLM and other tumor entities and its impact on anti-angiogenic anti-cancer therapy.
Role of OSCAR Signaling in Osteoclastogenesis and Bone Disease
Authors: Nedeva Iva R. , Vitale Mattia , Elson Ari , Hoyland Judith A. , Bella Jordi
Published: April 2021

Formation of mature bone-resorbing cells through osteoclastogenesis is required for the continuous remodeling and repair of bone tissue. In aging and disease this process may become aberrant, resulting in excessive bone degradation and fragility fractures. Interaction of receptor-activator of nuclear factor-κB (RANK) with its ligand RANKL activates the main signaling pathway for osteoclastogenesis. However, compelling evidence indicates that this pathway may not be sufficient for the production of mature osteoclast cells and that co-stimulatory signals may be required for both the expression of osteoclast-specific genes and the activation of osteoclasts. Osteoclast-associated receptor (OSCAR), a regulator of osteoclast differentiation, provides one such co-stimulatory pathway. This review summarizes our present knowledge of osteoclastogenesis signaling and the role of OSCAR in the normal production of bone-resorbing cells and in bone disease. Understanding the signaling mechanism through this receptor and how it contributes to the production of mature osteoclasts may offer a more specific and targeted approach for pharmacological intervention against pathological bone resorption.
Exosomal Non-coding RNAs-Mediated Crosstalk in the Tumor Microenvironment
Authors: Chen Qi , Li Yuefeng , Liu Yueqin , Xu Wenlin , Zhu Xiaolan
Published: April 2021

Exosomes are secreted by different types of cells in tumor microenvironment (TME) and participate in multiple biological processes of tumors. Non-coding RNAs (ncRNAs) enveloped in exosomes and released to the TME are shown to be involved in tumorigenesis and development, as well as act as important intracellular communication mediators. However, the understanding on the exact regulatory functions and substrates of exosomal RNA is still at an early stage. In this review, we provided an overview on recent studies on exosomes mediating the modulation of both tumor cells and immune cells, then summarized the exosomal ncRNAs [such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs)] secreted by tumor cells and stromal cells that exhibited potential capabilities to regulate tumor cell growth, progression, metastasis, drug resistance, and immune response. Our review may hopefully inspire a deeper understanding on the ncRNAs’ function as useful biomarkers for the diagnosis, prognosis, and as novel targets therapy for cancer.
Expression Level of ADAMTS1 in Granulosa Cells of PCOS Patients Is Related to Granulosa Cell Function, Oocyte Quality, and Embryo Development
Authors: Yang Guang , Yao Guidong , Xu Ziwen , Fan Huiying , Liu Xingui , He Jiahuan , Kong Yue , Kong Deqi , Bai Yucheng , He Qina , Zhang Tongwei , Zhang Junya , Sun Yingpu
Published: April 2021

A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1) is an extracellular matrix metalloproteinase that plays an important role in the process of ovulation. According to previous studies, the expression level of ADAMTS1 in the granulosa cells of polycystic ovarian syndrome (PCOS) patients and the mechanism for regulating oocyte quality and embryonic development potential are still unclear. Our research clarified that ADAMTS1 was significantly increased in granulosa cells of PCOS patients as compared to ovulatory controls. After silencing ADAMTS1 in granulosa cells, cell proliferation and E2 secretion were significantly inhibited, which may be related to the down-regulation of B-cell lymphoma 2 (Bcl2) family genes and key genes involved in E2 synthesis. Through retrospective analysis of the clinical data, it was found that the expression level of ADAMTS1 was significantly positively correlated to the oocyte maturation rate and good-quality embryo rate in PCOS patients. The downregulation of ADAMTS1 in primary granulosa cells lead to the changes in the expression of marker genes for oocyte and embryonic quality. By using immunofluorescence staining, it was found ADAMTS1 was expressed in various stages of pre-implantation embryo but its expression level gradually decreases with the development of the embryo. In addition, the silence of ADAMTS1 in 3PN zygotes significantly prolonged the development time of the zygote to the morula stage. This is, to our knowledge, the first time to explored the mechanism by which ADAMST1 is involved in affecting the quality of oocytes and embryonic development potential, which will provide new evidence for further understanding of the follicular microenvironment and embryo development.
Folding for the Immune Synapse: CCT Chaperonin and the Cytoskeleton
Authors: Martín-Cófreces Noa Beatriz , Valpuesta José María , Sánchez-Madrid Francisco
Published: April 2021

Lymphocytes rearrange their shape, membrane receptors and organelles during cognate contacts with antigen-presenting cells (APCs). Activation of T cells by APCs through pMHC-TCR/CD3 interaction (peptide-major histocompatibility complex-T cell receptor/CD3 complexes) involves different steps that lead to the reorganization of the cytoskeleton and organelles and, eventually, activation of nuclear factors allowing transcription and ultimately, replication and cell division. Both the positioning of the lymphocyte centrosome in close proximity to the APC and the nucleation of a dense microtubule network beneath the plasma membrane from the centrosome support the T cell’s intracellular polarity. Signaling from the TCR is facilitated by this traffic, which constitutes an important pathway for regulation of T cell activation. The coordinated enrichment upon T cell stimulation of the chaperonin CCT (chaperonin-containing tailless complex polypeptide 1; also termed TRiC) and tubulins at the centrosome area support polarized tubulin polymerization and T cell activation. The proteasome is also enriched in the centrosome of activated T cells, providing a mechanism to balance local protein synthesis and degradation. CCT assists the folding of proteins coming fromde novosynthesis, therefore favoring mRNA translation. The functional role of this chaperonin in regulating cytoskeletal composition and dynamics at the immune synapse is discussed.
Phosphorylation and Ubiquitylation Regulate Protein Trafficking, Signaling, and the Biogenesis of Primary Cilia
Authors: May Elena A. , Sroka Tommy J. , Mick David U.
Published: April 2021

The primary cilium is a solitary, microtubule-based membrane protrusion extending from the surface of quiescent cells that senses the cellular environment and triggers specific cellular responses. The functions of primary cilia require not only numerous different components but also their regulated interplay. The cilium performs highly dynamic processes, such as cell cycle-dependent assembly and disassembly as well as delivery, modification, and removal of signaling components to perceive and process external signals. On a molecular level, these processes often rely on a stringent control of key modulatory proteins, of which the activity, localization, and stability are regulated by post-translational modifications (PTMs). While an increasing number of PTMs on ciliary components are being revealed, our knowledge on the identity of the modifying enzymes and their modulation is still limited. Here, we highlight recent findings on cilia-specific phosphorylation and ubiquitylation events. Shedding new light onto the molecular mechanisms that regulate the sensitive equilibrium required to maintain and remodel primary cilia functions, we discuss their implications for cilia biogenesis, protein trafficking, and cilia signaling processes.
Feedback-Driven Mechanisms Between Phosphorylated Caveolin-1 and Contractile Actin Assemblies Instruct Persistent Cell Migration
Authors: Shi Xuemeng , Wen Zeyu , Wang Yajun , Liu Yan-Jun , Shi Kun , Jiu Yaming
Published: April 2021

The actin cytoskeleton and membrane-associated caveolae contribute to active processes, such as cell morphogenesis and motility. How these two systems interact and control directional cell migration is an outstanding question but remains understudied. Here we identified a negative feedback between contractile actin assemblies and phosphorylated caveolin-1 (CAV-1) in migrating cells. Cytoplasmic CAV-1 vesicles display actin-associated motilities by sliding along actin filaments or/and coupling to do retrograde flow with actomyosin bundles. Inhibition of contractile stress fibers, but not Arp2/3-dependent branched actin filaments, diminished the phosphorylation of CAV-1 on site Tyr14, and resulted in substantially increased size and decreased motility of cytoplasmic CAV-1 vesicles. Reciprocally, both the CAV-1 phospho-deficient mutation on site Tyr14 and CAV-1 knockout resulted in dramatic AMPK phosphorylation, further causing reduced active level of RhoA-myosin II and increased active level of Rac1-PAK1-Cofilin, consequently led to disordered contractile stress fibers and prominent lamellipodia. As a result, cells displayed depolarized morphology and compromised directional migration. Collectively, we propose a model in which feedback-driven regulation between actin and CAV-1 instructs persistent cell migration.
Autophagic Organelles in DNA Damage Response
Authors: Kim Jeongha , Lee Sungmin , Kim Hyunwoo , Lee Haksoo , Seong Ki Moon , Youn HyeSook , Youn BuHyun
Published: April 2021

Autophagy is an important subcellular event engaged in the maintenance of cellular homeostasis via the degradation of cargo proteins and malfunctioning organelles. In response to cellular stresses, like nutrient deprivation, infection, and DNA damaging agents, autophagy is activated to reduce the damage and restore cellular homeostasis. One of the responses to cellular stresses is the DNA damage response (DDR), the intracellular pathway that senses and repairs damaged DNA. Proper regulation of these pathways is crucial for preventing diseases. The involvement of autophagy in the repair and elimination of DNA aberrations is essential for cell survival and recovery to normal conditions, highlighting the importance of autophagy in the resolution of cell fate. In this review, we summarized the latest information about autophagic recycling of mitochondria, endoplasmic reticulum (ER), and ribosomes (called mitophagy, ER-phagy, and ribophagy, respectively) in response to DNA damage. In addition, we have described the key events necessary for a comprehensive understanding of autophagy signaling networks. Finally, we have highlighted the importance of the autophagy activated by DDR and appropriate regulation of autophagic organelles, suggesting insights for future studies. Especially, DDR from DNA damaging agents including ionizing radiation (IR) or anti-cancer drugs, induces damage to subcellular organelles and autophagy is the key mechanism for removing impaired organelles.
Activable Multi-Modal Nanoprobes for Imaging Diagnosis and Therapy of Tumors
Authors: Yang Yan , Yue Saisai , Qiao Yuanyuan , Zhang Peisen , Jiang Ni , Ning Zhenbo , Liu Chunyan , Hou Yi
Published: April 2021

Malignant tumors have become one of the major causes of human death, but there remains a lack of effective methods for tiny tumor diagnosis, metastasis warning, clinical efficacy prediction, and effective treatment. In this context, localizing tiny tumors via imaging and non-invasively extracting molecular information related to tumor proliferation, invasion, metastasis, and drug resistance from the tumor microenvironment have become the most fundamental tasks faced by cancer researchers. Tumor-associated microenvironmental physiological parameters, such as hypoxia, acidic extracellular pH, protease, reducing conditions, and so forth, have much to do with prognostic indicators for cancer progression, and impact therapeutic administrations. By combining with various novel nanoparticle-based activatable probes, molecular imaging technologies can provide a feasible approach to visualize tumor-associated microenvironment parameters noninvasively and realize accurate treatment of tumors. This review focuses on the recent achievements in the design of “smart” nanomedicine responding to the tumor microenvironment-related features and highlights state-of- the-art technology in tumor imaging diagnosis and therapy.
Chemical Glycosylation and Its Application to Glucose Homeostasis-Regulating Peptides
Authors: Chandrashekar Chaitra , Hossain Mohammed Akhter , Wade John D.
Published: April 2021

Peptides and proteins are attractive targets for therapeutic drug development due to their exquisite target specificity and low toxicity profiles. However, their complex structures give rise to several challenges including solubility, stability, aggregation, low bioavailability, and poor pharmacokinetics. Numerous chemical strategies to address these have been developed including the introduction of several natural and non-natural modifications such as glycosylation, lipidation, cyclization and PEGylation. Glycosylation is considered to be one of the most useful modifications as it is known to contribute to increasing the stability, to improve solubility, and increase the circulating half-lifves of these biomolecules. However, cellular glycosylation is a highly complex process that generally results in heterogenous glycan structures which confounds quality control and chemical and biological assays. For this reason, much effort has been expended on the development of chemical methods, including by solid phase peptide synthesis or chemoenzymatic processes, to enable the acquisition of homogenous glycopeptides to greatly expand possibilities in drug development. In this mini-review, we highlight the importance of such chemical glycosylation methods for improving the biophysical properties of naturally non-glycosylated peptides as applied to the therapeutically essential insulin and related peptides that are used in the treatment of diabetes.
A pH-Responsive Supramolecular Drug Delivery System Constructed by Cationic Pillar[5]arene for Enhancing Antitumor Activity
Authors: Liu Luzhi , Zhou Qingqing , He Qin , Duan Wengui , Huang Yan
Published: April 2021

Drug delivery systems have good biocompatibiliy and low side effects for cancer treatment, but overcoming high efficiency of drug-loading and the drug-targeting controlled release still remains challenging. In this work, supramolecular vesicles, with pH-triggering effect, have been successfully constructed for drug delivery, which are fabricated by the complexation between a cationic pillar[5]arene (DAWP5) and a sodium dodecyl sulfonate (SDS) in aqueous solution. Drug-loading and releasing results demonstrated that anticancer drug doxorubicin (DOX) could be loaded efficiently by such cationic vesicles in neutral condition, and the drug release could be controlled in the simulated weak acid environment of tumor cells. Moreover, the vesicles had low cytotoxicity to normal human cell (L02), while the DOX-loaded vesicles could significantly enhance the cytotoxicity of free DOX for normal cell L02 and four tested tumor cells (Hela, HepG2, MGC-803 and T24). Especially for HepG2, after 24 h incubation time, IC50 of DOX-loaded vesicles was only 0.79 μM, about 23% of that of DOX (3.43 μM). These results suggested that such novel vesicles have promising potential to construct nano-drug delivery systems for various biomedical applications.
HIV-1 Impact on Malaria Transmission: A Complex and Relevant Global Health Concern
Authors: Roberds Ashleigh , Ferraro Emily , Luckhart Shirley , Stewart V. Ann
Published: April 2021

Malaria/HIV-1 co-infection has become a significant public health problem in the tropics where there is geographical overlap of the two diseases. It is well described that co-infection impacts clinical progression of both diseases; however, less is known about the impact of co-infection on disease transmission. Malaria transmission is dependent upon multiple critical factors, one of which is the presence and viability of the sexual-stage gametocyte. In this review, we summarize evidence surrounding gametocyte production in Plasmodium falciparum and the development factors and the consequential impact that HIV-1 has on malaria parasite transmission. Epidemiological and clinical evidence surrounding anemia, immune dysregulation, and chemotherapy as it pertains to co-infection and gametocyte transmission are reviewed. We discuss significant gaps in understanding that are often due to the biological complexities of both diseases as well as the lack of entomological data necessary to define transmission success. In particular, we highlight special epidemiological populations, such as co-infected asymptomatic gametocyte carriers, and the unique role these populations have in a future focused on malaria elimination and eradication.