bluuebunny/crossref_metadata_2025 huggingface dataset:
Ailevi Akdeniz Ateşi Hastalığında Aksiyel Spondiloartrit Alt Grupları Arasında Klinik Bulguların ve Patojen Mutasyonların Karşılaştırılması
Authors: AYAR Koray , ERMURAT Selime , TOKA Dilara , KÖSEGİL ÖZTÜRK Esra
Published: March 2021

Bu çalışmada, Ailevi Akdeniz ateşi (FMF) hastalığı olan radyografik olan ve olmayan aksiyel spondiloartrit (aks-SpA) hastaları arasında, Akdeniz Ateşi (MEFV) gen mutasyonlarının ve FMF ilişkili klinik bulguların karşılaştırılması amaçlanmıştır. Çalışmada Ocak 2015-Temmuz 2020 tarihleri arasında FMF hastalığı tanısı ile takip edilmekte olan hastaların dosyaları retrospektif olarak incelendi. Hastaların genetik tetkikleri, klinik bulguları ve sakroilyak eklemin röntgen ve manyetik rezonans görüntüleme tetkikleri incelendi. Uluslararası Spondiloartrit Değerlendirme Birliği (ASAS) kriterlerine göre aks-SpA hastaları radyografik olan ve olmayan şeklinde gruplandırılarak çalışmaya dahil edildi ve bulgular gruplar arasında karşılaştırıldı. Aks-SpA tespit edilen toplam 36 hasta (24 radyografik, 12 radyografik olmayan) çalışmaya dahil edildi. Test sonuçlarına ulaşılabilen 11 aks-SpA hastasının hepsinde insan lökosit antijeni (HLA)B27 genetik test sonucu negatif bulundu. Radyografik olan ve olmayan aks-SpA hastaları arasında klinik bulgular, kolşisin yanıtı ve aile öyküsü farklı değildi. M694V mutasyonunun fenotipik frekansı radyografik olan ve olmayan aks-SpA grupları arasında sırasıyla, %91,7 ve %50,0 bulundu (p=0,005). V726A mutasyonunun fenotipik frekansı radyografik olan ve olmayan aks-SpA grupları arasında sırasıyla, %0 ve %25,0 bulundu (p=0,011). Sonuç olarak FMF’ye eşlik eden aks-SpA’nın alt grupları arasında FMF klinik bulguları farklı değildir. M694V mutasyonu röntgen bulgularının belirgin olduğu SpA alt grubunda, V726A mutasyonu da röntgen bulguları belirgin olmayan SpA alt grubunda daha sıktırlar ve bu mutasyonlar sık görüldükleri SpA alt gruplarının etyolojisinde rol oynuyor olabilirler.
Anti-Inflammatory of Papaya Leaf Extract (Carica Papaya L) Towards Membrane Stabilization of Red Blood Cells
Authors: Kamilla Laila , Tumpuk Sri , Salim Maulidiyah
Published: March 2021

Traditional medical plants are known to society long ago. Apart from easily obtained and inexpensive, it can cure diseases with few side effects than modern medicine. Papaya leaves were used not only because of contained various chemical compounds with pharmacological effects but also alkaloids, flavonoids, saponins, and tannins compounds indicated as anti-inflammatory. This study applied a quasi-experimental design to test the papaya leaves anti-inflammatory activity. The red blood cell stabilization method was employed because analogous to the lysosomal membrane affected the inflammatory process. Purposive sampling was used, creating papaya leaves extract of 50 ppm, 100 ppm, 200 ppm, 400 ppm, 600 ppm, and 800 ppm concentration, made 24 total samples by four times replication. Based on the red blood cell lysis inhibition, the anti-inflammatory activity was measured and was compared with the positive control (diclofenac sodium). The papaya methanol extract result showed the highest anti-inflammatory activity at 800 ppm of 74.29%. The most effective concentration was at 200 ppm of 62.19%. Tukey's test showed p1.000 ≥ 0.05, suggesting H0 was accepted. There was no difference between the anti-inflammatory activity of papaya leaf methanol extract and diclofenac sodium showing stabilization of red blood cell membranes, indicating papaya potentially as an anti-inflammatory.
Exploring Psychological Condition of Breast Cancer Survivor After Mastectomy and Chemotherapy
Authors: Werdani Yesiana Dwi Wahyu , Prasetya Arief Widya
Published: March 2021

Breast cancer becomes a frightening disease for women, it is not only physically painful but also causes psychological disorders. This study aimed to explore the psychological condition of breast cancer survivors after mastectomy and chemotherapy. This was a qualitative study with thematic analysis methods. Samples were 20 breast cancer survivors taken by purposive sampling technique based on inclusion criteria from three community health centers in Surabaya Indonesia. Ethical requirements are completed before data collection. Data collection using an in-depth interview technique and recorded by a voice recorder. Content analysis is used to process the data. This study found 2 main themes hopelessness and negative psychological well-being. On the first main theme, there was 4 sub-theme consist of worthlessness, purposeless in life, pessimistic, unhappy. While on the second main theme there were 6 sub-theme consist of worried, negative thought, irritable, negative relationship with others, denial, felt guilty. Breast cancer survivors after mastectomy and chemotherapy experience a variety of sufferings on the psychological condition and could not be able to see other good things in their life.
The Calculation of The Need for Medical Record Personel Based on The Full-Time Equivalent Method in The Outpatient Registration Department of Public Health Center
Authors: Adi Sapto , Mawarni Dian , Istiqomah Siti
Published: March 2021

Public health center X is one of the public health center with high outpatient loads in Malang City. On average, the daily amount of outpatients is 119. The high load of outpatient directly affects employee’s working load. One of the units considered susceptible to working load increase is the medical record unit at the registration department because they have to interact with all visiting patients. The study aimed to discover the need for medical record personnel at the outpatient registration department of public health center X using the Full-Time Equivalent (FTE) method. The study used a descriptive study design and a quantitative approach. The researchers utilized a total sampling technique with two medical record personnel at the outpatient registration department. The study instrument employed was the outpatient registration daily log of Public health center X. The study results show that the working load of medical record personnel at the BPJS patient registration department had an FTE index value of 2.24 > 1.28, categorized as overload. Meanwhile, medical record personnel at the non-BPJS patient registration department had an FTE index value of 0.96 < 0.99, categorized as underload. Therefore, it can be concluded that Public health center X requires two additional medical record personnel at the BPJS patient registration department, while the non-BPJS patient registration department did not require additional medical record personnel.
A GEOGRAFIA DO ACESSO AO SERVIÇO DE ORIENTAÇÃO TÉCNICA PELOS AGRICULTORES FAMILIARES NO BRASIL E NO ESTADO DE GOIÁS: UMA ANÁLISE ESPAÇO-TEMPORAL DOS DADOS DOS CENSOS AGROPECUÁRIOS DE 2006 E 2017
Authors: Diniz Raphael Fernando , Clemente Evandro Cesar
Published: March 2021

Buscou-se analisar, no presente artigo, em que medida a Política Nacional de Assistência Técnica e Extensão Rural (PNATER) provocou mudanças nos índices de acesso à orientação técnica no seu principal público beneficiário, que são os agricultores familiares, bem como se promoveu a transição agroecológica no campo. Para isso, recorremos à análise de um conjunto de dados dos Censos Agropecuários do Instituto Brasileiro de Geografia e Estatística (IBGE) de 2006 e 2017. O recorte espacial de investigação compreendeu o Brasil e o estado de Goiás. Em que pese os expressivos investimentos feitos pelo Governo Federal a partir dos anos 2.000, a transição agroecológica nos sistemas de produção agropecuária e a universalização e democratização do acesso aos serviços de orientação técnica estão longe de se tornarem realidade para considerável parte dos agricultores familiares.
PENGUJIAN WAGNER'S LAW VERSUS KEYNESIAN HYPOTHESIS: PENDEKATAN REGIONAL INDONESIA
Authors: Pasaribu Esti , Septriani Septriani
Published: March 2021

In this paper, we tested the Wagner’s Law against the Keynesian Hypothesis for Indonesia using granger causality test. After conducting theoretical and empirical theory, this paper is analysing the relationship between government expenditure and GDP percapita. The long run parameters and causality test found valid Wagners’ Law in Indonesia not Keynesian Hypothesis. The results reveal a positive and statistically significant long run effect running from economic growth toward the government expenditure refer to Wagner’s Law in Indonesia. Further more, the growth of population is giving a positive effect for government expenditure also.
Perfeccionismo e a relação com psicopatologias: Estudo integrativo
Authors: Rocha André Sousa
Published: March 2021

O perfeccionismo é um traço latente psicológico que vem sendo compreendido de diferentes formas. Os avanços científicos e metodológicos na área sugerem que esse fenômeno possui componentes positivos e negativos. Esse estudo motivou-se pela questão problema levantada: quais as principais psicopatologias, na atualidade, relacionadas ao perfeccionismo? Algumas discussões são promovidas nesse ponto de vista. Para tanto, o presente artigo condensa, organiza e apresenta uma revisão integrativa consultada em bases nacionais e internacionais e visou investigar quais as principais psicopatologias relacionadas ao perfeccionismo. Desse modo, foram executadas buscas de artigos nas bases de dados Medline, Pubmed e Springer com os descritores perfeccionismo, psicopatologia, perfectionism  e psychopathology ambos recrutados do DeCS e MeSH. Dos 226 artigos encontrados inicialmente, 213 foram descartados à medida que os critérios de inclusão e exclusão iam sendo aplicados. Desse modo, 13 artigos compuseram a amostra final. Os resultados indicaram que o perfeccionismo tem se relacionado com depressão, ansiedade, transtornos alimentares (bulimia e anorexia) bem como transtorno obsessivo compulsivo. Limitações e sugestões de futuros estudos são discutidos ao final.
Burnout e fatores associados entre profissionais de enfermagem de hospital municipal
Authors: Soares Rafael da Silva , Teixeira Enéas Rangel , Silva Jorge Luiz Lima da , Chagas Marléa Crescêncio
Published: March 2021

Objetivo: descrever a prevalência e possíveis fatores associados à síndrome de burnout entre profissionais de enfermagem de unidade de terapia intensiva. Metodologia: estudo epidemiológico observacional, descritivo, seccional. A população foi composta por amostra de 85 profissionais de enfermagem dos setores de terapia intensiva de hospital público municipal. Foi utilizada a versão traduzida e validada para o português do Maslach Burnout Inventory. Foi realizada análise estatística descritiva com medidas de tendência central, de dispersão e análise de frequência. A coleta de dados ocorreu em janeiro de 2018. Resultados: a prevalência de suspeição da síndrome de burnout foi de 40%, sendo que 24,7% apresentaram esgotamento emocional alto, 18,8% despersonificação elevada, e 08,2% realização profissional baixa. Ter cursado ensino superior (p=0,028), profissional enfermeiro (p=0,009) e sentir-se estressado no trabalho (p=0,001), apresentaram associação com a síndrome. Conclusão: A síndrome de burnout pode ser desencadeada por diferentes fatores: ambiente de trabalho; organizacionais, personalidade, relacionamentos. É necessário adotar medidas preventivas e controle de doenças relacionadas ao estresse laboral.
Colégio Pedro II: Um estudo sobre legislação e indicadores aplicados
Authors: Neves Ricardo Dias das , Almeida Adjovanes Thadeu Silva de
Published: March 2021

Criado no ano de 1837, o Colégio Pedro II tem sua área de atuação desde a Educação Infantil até a Pós-Graduação Stricto Senso. A Lei 11.892 de 2008 criou os Institutos Federais e teve sua redação atualizada pela Lei 12.677 de 2012, incluindo o Colégio Pedro II na Rede Federal de Educação, Científica, Profissional e Tecnológica. A Lei 12.677/12 manteve a tradicional denominação de “Colégio Pedro II”, equiparando-o, contudo, à condição de Instituto Federal de Educação, Ciência e Tecnologia. O artigo, aborda, principalmente, os aspectos legais desta equiparação, explicando conceitos jurídicos e comentando os principais artigos da legislação pertinente, além de analisar relevantes indicadores econômicos e sociais da instituição.
EKSISTENSI HUKUM JAMINAN DALAM PROGRAM PEMULIHAN EKONOMI NASIONAL (PEN) PADA MASA PANDEMI COVID-19
Authors: Ernawati Elisatin , Syaifudin Ahmad
Published: March 2021

Pelaksanaan program pemerintah dalam upaya Pemulihan Ekonomi Nasional sebagaimana yang telah dirumuskan dalam PP No. 23 / 2020, telah memasukkan program penjaminan sebagai salah satu skema yang berkontribusi dominan dalam keberhasilan program. Eksistensi hukum jaminan menjadi dipertanyakan sejauh mana dapat mengambil peran termasuk partisipasi Notaris dalam menjalan peran dan wewenangnya. Dalam penelitian ini penulis menggunakan metode penelitian yuridis normatif dengan memakai pendekatan konsep (conceptual approach), perundang-undangan (Statute Approach) dan pendekatan kasus (Case Approach). dari penelitian dapat disimpulkan bahwa jaminan dalam prespektif hukum jaminan membagi dalam bentuk jaminan kebendaan dan penanggungan telah berkembang dengan sangat cepat. Jaminan kebendaan yang membatasi nilai obyek jaminan berkembang sesuai dengan regulasi, sedangkan jaminan penanggungan (jaminan personal, korporasi) berkembang sesuai dengan perkembangan ekonomi dan bisnis. Keberadaan Notaris dalam kondisi apapun tetap mengambil peran sentral sesuai dengan tugas dan kewenangan terutama dalam merumuskan perjanjian pokok dan tambahan sebagai akta otentik yang mengikat para pihak.Kata kunci : PEN, Hukum Jaminan, Notaris Implementation of government programs in efforts to restore the National Economy as formulated in PP. 23/2020, has included the guarantee program as one of the schemes that have contributed dominantly to the success of the program. The existence of guarantee law becomes questionable to what extent it can take a role, including the participation of a notary in carrying out its functions and its authority. In this study the authors used a normative juridical research method using a conceptual approach, statutory approach and a case approach. From the research it can be concluded that guarantees in the perspective of security law divides into the form of property guarantees and coverage has grown very rapidly. Material guarantees that limit the value of the object of guarantee develop in accordance with regulations, while security guarantees (personal, corporate guarantees) develop according to economic and business developments. The existence of a Notary in any condition still plays a central role in accordance with the duties and authorities, especially in formulating the main and additional agreements as authentic deeds that bind the parties.Keywords: PEN, Guarantee Law, Notary
Sea urchin mass mortality rapidly restores kelp forest communities
Authors: Williams JP , Claisse JT , Pondella II DJ , Williams CM , Robart MJ , Scholz Z , Jaco EM , Ford T , Burdick H , Witting D
Published: March 2021

Giant kelp Macrocystis pyrifera is a foundational species that forms a 3-dimensional habitat and supports numerous high-value fisheries species. Constant grazing of kelp holdfasts by overabundant sea urchins causes catastrophic ecological and economic impacts on rocky reefs worldwide. Overgrazing creates urchin barrens that persist for decades in the absence of ecological forcing that would shift the ecosystem back to a kelp-dominated state. Annual surveys of kelp forest and urchin barren sites in the Southern California Bight were performed from 2011 to 2020 to assess changes in kelp forest communities as a result of restoration efforts through sea urchin culling. However, that time period also encompassed a sea urchin mass mortality event. Following drastic reductions of sea urchin densities, rocky reefs returned to a kelp-dominated state within approximately 6 mo and remained stable through the remainder of the study. Benthic cover, fish, and kelp and macroinvertebrate communities inside former urchin barrens became more similar to that of kelp forest reference sites and continued to do so for the next 5 yr. Giant kelp density increased significantly compared to existing kelp forests, while benthic indicators of urchin dominance (i.e. crustose coralline algae and bare rock cover) decreased. Kelp restoration through sea urchin culling essentially mimics sea urchin mass mortality events. If culling can produce similar declines in urchin density, it may be a viable management tool to rapidly restore persistent urchin barrens at moderate spatial scales, while a mass mortality event can drive recovery of kelp forest communities at more extensive spatial scales.
In the Right Place at the Right Time: Regulation of Cell Metabolism by IP3R-Mediated Inter-Organelle Ca2+ Fluxes
Authors: Ahumada-Castro Ulises , Bustos Galdo , Silva-Pavez Eduardo , Puebla-Huerta Andrea , Lovy Alenka , Cárdenas César
Published: March 2021

In the last few years, metabolism has been shown to be controlled by cross-organelle communication. The relationship between the endoplasmic reticulum and mitochondria/lysosomes is the most studied; here, inositol 1,4,5-triphosphate (IP3) receptor (IP3R)-mediated calcium (Ca2+) release plays a central role. Recent evidence suggests that IP3R isoforms participate in synthesis and degradation pathways. This minireview will summarize the current findings in this area, emphasizing the critical role of Ca2+communication on organelle function as well as catabolism and anabolism, particularly in cancer.
Thermodynamics and Kinetics of Sulfuric Acid Leaching Transformation of Rare Earth Fluoride Molten Salt Electrolysis Slag
Authors: Chen Lijie , Xu Jiacong , Yu Xiaoqiang , Tian Lei , Wang Ruixiang , Xu Zhifeng
Published: March 2021

Rare earth element recovery in molten salt electrolysis is approximately between 91 and 93%, whereof 8% is lost in waste molten salt slag. Presently, minimal research has been conducted on the technology for recycling waste rare earth molten salt slag, which is either discarded as industrial garbage or mixed with waste slag into qualified molten salt. The development of a new approach toward the effective treatment of rare earth fluoride molten salt electrolytic slag, which can recycle the remaining rare earth and improve the utilization rate, is essential. Herein, weak magnetic iron separation, sulfuric acid leaching transformation, water leaching, hydrogen fluoride water absorption, and cycle precipitation of rare earth are used to recover rare earth from their fluoride molten salt electrolytic slag, wherein the thermodynamic and kinetic processes of sulfuric acid leaching transformation are emphatically studied. Thermodynamic results show that temperature has a great influence on sulfuric acid leaching. With rising temperature, the equilibrium constant of the reaction gradually increases, and the stable interval of NdF3 decreases, while that of Nd3+ increases, indicating that high temperature is conducive to the sulfuric acid leaching process, whereof the kinetic results reveal that the activation energy E of Nd transformation is 41.57 kJ/mol, which indicates that the sulfuric acid leaching process is controlled by interfacial chemical reaction. According to the Nd transformation rate equation in the sulfuric acid leaching process of rare earth fluoride molten salt electrolytic slag under different particle size conditions, it is determinable that with the decrease of particle size, the reaction rate increases accordingly, while strengthening the leaching kinetic process. According to the equation of Nd transformation rate in the sulfuric acid leaching process under different sulfuric acid concentration conditions, the reaction series of sulfuric acid concentration K = 6.4, which is greater than 1, indicating that increasing sulfuric acid concentration can change the kinetic-control region and strengthen the kinetic process.
Identification of Deep-Intronic Splice Mutations in a Large Cohort of Patients With Inherited Retinal Diseases
Authors: Qian Xinye , Wang Jun , Wang Meng , Igelman Austin D. , Jones Kaylie D. , Li Yumei , Wang Keqing , Goetz Kerry E. , Birch David G. , Yang Paul , Pennesi Mark E. , Chen Rui
Published: March 2021

High throughput sequencing technologies have revolutionized the identification of mutations responsible for a diverse set of Mendelian disorders, including inherited retinal disorders (IRDs). However, the causal mutations remain elusive for a significant proportion of patients. This may be partially due to pathogenic mutations located in non-coding regions, which are largely missed by capture sequencing targeting the coding regions. The advent of whole-genome sequencing (WGS) allows us to systematically detect non-coding variations. However, the interpretation of these variations remains a significant bottleneck. In this study, we investigated the contribution of deep-intronic splice variants to IRDs. WGS was performed for a cohort of 571 IRD patients who lack a confident molecular diagnosis, and potential deep intronic variants that affect proper splicing were identified using SpliceAI. A total of six deleterious deep intronic variants were identified in eight patients. An in vitro minigene system was applied to further validate the effect of these variants on the splicing pattern of the associated genes. The prediction scores assigned to splice-site disruption positively correlated with the impact of mutations on splicing, as those with lower prediction scores demonstrated partial splicing. Through this study, we estimated the contribution of deep-intronic splice mutations to unassigned IRD patients and leveraged in silico and in vitro methods to establish a framework for prioritizing deep intronic variant candidates for mechanistic and functional analyses.
Spliceosomal snRNA Epitranscriptomics
Authors: Morais Pedro , Adachi Hironori , Yu Yi-Tao
Published: March 2021

Small nuclear RNAs (snRNAs) are critical components of the spliceosome that catalyze the splicing of pre-mRNA. snRNAs are each complexed with many proteins to form RNA-protein complexes, termed as small nuclear ribonucleoproteins (snRNPs), in the cell nucleus. snRNPs participate in pre-mRNA splicing by recognizing the critical sequence elements present in the introns, thereby forming active spliceosomes. The recognition is achieved primarily by base-pairing interactions (or nucleotide-nucleotide contact) between snRNAs and pre-mRNA. Notably, snRNAs are extensively modified with different RNA modifications, which confer unique properties to the RNAs. Here, we review the current knowledge of the mechanisms and functions of snRNA modifications and their biological relevance in the splicing process.
Cervicovaginal Immune Activation in Zambian Women With Female Genital Schistosomiasis
Authors: Sturt Amy S. , Webb Emily L. , Patterson Catriona , Phiri Comfort R. , Mweene Tobias , Kjetland Eyrun F. , Mudenda Maina , Mapani Joyce , Mutengo Mable M. , Chipeta James , van Dam Govert J. , Corstjens Paul L. A. M. , Ayles Helen , Hayes Richard J. , Hansingo Isaiah , Cools Piet , van Lieshout Lisette , Helmby Helena , McComsey Grace A. , Francis Suzanna C. , Bustinduy Amaya L.
Published: March 2021

HIV-1 infection disproportionately affects women in sub-Saharan Africa, where areas of high HIV-1 prevalence andSchistosoma haematobiumendemicity largely overlap. Female genital schistosomiasis (FGS), an inflammatory disease caused byS. haematobiumegg deposition in the genital tract, has been associated with prevalent HIV-1 infection. Elevated levels of the chemokines MIP-1α (CCL-3), MIP-1β (CCL-4), IP-10 (CXCL-10), and IL-8 (CXCL-8) in cervicovaginal lavage (CVL) have been associated with HIV-1 acquisition. We hypothesize that levels of cervicovaginal cytokines may be raised in FGS and could provide a causal mechanism for the association between FGS and HIV-1. In the cross-sectional BILHIV study, specimens were collected from 603 female participants who were aged 18–31 years, sexually active, not pregnant and participated in the HPTN 071 (PopART) HIV-1 prevention trial in Zambia. Participants self-collected urine, and vaginal and cervical swabs, while CVLs were clinically obtained. Microscopy andSchistosomacirculating anodic antigen (CAA) were performed on urine. Genital samples were examined for parasite-specific DNA by PCR. Women with FGS (n=28), defined as a positiveSchistosomaPCR from any genital sample were frequency age-matched with 159 FGS negative (defined as negativeSchistosomaPCR, urine CAA, urine microscopy, and colposcopy imaging) women. Participants with probable FGS (n=25) (defined as the presence of either urine CAA or microscopy in combination with one of four clinical findings suggestive of FGS on colposcope-obtained photographs) were also included, for a total sample size of 212. The concentrations of 17 soluble cytokines and chemokines were quantified by a multiplex bead-based immunoassay. There was no difference in the concentrations of cytokines or chemokines between participants with and without FGS. An exploratory analysis of those women with a higher FGS burden, defined by ≥2 genital specimens with detectableSchistosomaDNA (n=15) showed, after adjusting for potential confounders, a higher Th2 (IL-4, IL-5, and IL-13) and pro-inflammatory (IL-15) expression pattern in comparison to FGS negative women, with differences unlikely to be due to chance (p=0.037 for IL-4 and p<0.001 for IL-5 after adjusting for multiple testing). FGS may alter the female genital tract immune environment, but larger studies in areas of varying endemicity are needed to evaluate the association with HIV-1 vulnerability.
Translational Research in Vitiligo
Authors: Katz Erica L. , Harris John E.
Published: March 2021

Vitiligo is a disease of the skin characterized by the appearance of white spots. Significant progress has been made in understanding vitiligo pathogenesis over the past 30 years, but only through perseverance, collaboration, and open-minded discussion. Early hypotheses considered roles for innervation, microvascular anomalies, oxidative stress, defects in melanocyte adhesion, autoimmunity, somatic mosaicism, and genetics. Because theories about pathogenesis drive experimental design, focus, and even therapeutic approach, it is important to consider their impact on our current understanding about vitiligo. Animal models allow researchers to perform mechanistic studies, and the development of improved patient sample collection methods provides a platform for translational studies in vitiligo that can also be applied to understand other autoimmune diseases that are more difficult to study in human samples. Here we discuss the history of vitiligo translational research, recent advances, and their implications for new treatment approaches.
Adoptive Transfer of Regulatory Immune Cells in Organ Transplantation
Authors: Oberholtzer Nathaniel , Atkinson Carl , Nadig Satish N.
Published: March 2021

Chronic graft rejection remains a significant barrier to solid organ transplantation as a treatment for end-organ failure. Patients receiving organ transplants typically require systemic immunosuppression in the form of pharmacological immunosuppressants for the duration of their lives, leaving these patients vulnerable to opportunistic infections, malignancies, and other use-restricting side-effects. In recent years, a substantial amount of research has focused on the use of cell-based therapies for the induction of graft tolerance. Inducing or adoptively transferring regulatory cell types, including regulatory T cells, myeloid-derived suppressor cells, and IL-10 secreting B cells, has the potential to produce graft-specific tolerance in transplant recipients. Significant progress has been made in the optimization of these cell-based therapeutic strategies as our understanding of their underlying mechanisms increases and new immunoengineering technologies become more widely available. Still, many questions remain to be answered regarding optimal cell types to use, appropriate dosage and timing, and adjuvant therapies. In this review, we summarize what is known about the cellular mechanisms that underly the current cell-based therapies being developed for the prevention of allograft rejection, the different strategies being explored to optimize these therapies, and all of the completed and ongoing clinical trials involving these therapies.
Direct LC-MS/MS Analysis of Extra- and Intracellular Glycerophosphoinositol in Model Cancer Cell Lines
Authors: Campos Ana Margarida , Nuzzo Genoveffa , Varone Alessia , Italiani Paola , Boraschi Diana , Corda Daniela , Fontana Angelo
Published: March 2021

Glycerophosphoinositols (GPIs) are water-soluble bioactive phospholipid derivatives of increasing interest as intracellular and paracrine mediators of eukaryotic cell functions. The most representative compound of the family is glycerophosphoinositol (GroPIns), an ubiquitous component of mammalian cells that participates in cell proliferation, cell survival and cell response to stimuli. Levels and activity of this compound vary among cell types and deciphering these functions requires accurate measurements in in vitro and in vivo models. The conventional approaches for the analysis of GroPIns pose several issues in terms of sensitivity and product resolution, especially when the product is in the extracellular milieu. Here we present an UPLC-MS study for the quantitative analysis of this lipid derivative in cells and, for the first time, culture supernatants. The method is based on a solid-phase extraction that allows for fast desalting and analyte concentration. The robustness of the procedure was tested on the simultaneous measurements of intra- and extracellular levels of GroPIns in a number of human cell lines where it has been shown that the non-transformed cells are characterized by high extracellular level of GroPIns, whereas the tumor cells tended to have higher intracellular levels.
Effects of Ocean Acidification on Calcification of the Sub-Antarctic Pteropod Limacina retroversa
Authors: Mekkes Lisette , Sepúlveda-Rodríguez Guadalupe , Bielkinaitė Gintarė , Wall-Palmer Deborah , Brummer Geert-Jan A. , Dämmer Linda K. , Huisman Jef , van Loon Emiel , Renema Willem , Peijnenburg Katja T. C. A.
Published: March 2021

Ocean acidification is expected to impact the high latitude oceans first, as CO2 dissolves more easily in colder waters. At the current rate of anthropogenic CO2 emissions, the sub-Antarctic Zone will start to experience undersaturated conditions with respect to aragonite within the next few decades, which will affect marine calcifying organisms. Shelled pteropods, a group of calcifying zooplankton, are considered to be especially sensitive to changes in carbonate chemistry because of their thin aragonite shells. Limacina retroversa is the most abundant pteropod in sub-Antarctic waters, and plays an important role in the carbonate pump. However, not much is known about its response to ocean acidification. In this study, we investigated differences in calcification between L. retroversa individuals exposed to ocean carbonate chemistry conditions of the past (pH 8.19; mid-1880s), present (pH 8.06), and near-future (pH 7.93; predicted for 2050) in the sub-Antarctic. After 3 days of exposure, calcification responses were quantified by calcein staining, shell weighing, and Micro-CT scanning. In pteropods exposed to past conditions, calcification occurred over the entire shell and the leading edge of the last whorl, whilst individuals incubated under present and near-future conditions mostly invested in extending their shells, rather than calcifying over their entire shell. Moreover, individuals exposed to past conditions formed larger shell volumes compared to present and future conditions, suggesting that calcification is already decreased in today’s sub-Antarctic waters. Shells of individuals incubated under near-future conditions did not increase in shell weight during the incubation, and had a lower density compared to past and present conditions, suggesting that calcification will be further compromised in the future. This demonstrates the high sensitivity of L. retroversa to relatively small and short-term changes in carbonate chemistry. A reduction in calcification of L. retroversa in the rapidly acidifying waters of the sub-Antarctic will have a major impact on aragonite-CaCO3 export from oceanic surface waters to the deep sea.
Quorum Sensing-Mediated and Growth Phase-Dependent Regulation of Metabolic Pathways in Hafnia alvei H4
Authors: Yan Congyang , Li Xue , Zhang Gongliang , Zhu Yaolei , Bi Jingran , Hao Hongshun , Hou Hongman
Published: March 2021

Quorum sensing (QS) is a widespread regulatory mechanism in bacteria used to coordinate target gene expression with cell density. Thus far, little is known about the regulatory relationship between QS and cell density in terms of metabolic pathways in Hafnia alvei H4. In this study, transcriptomics analysis was performed under two conditions to address this question. The comparative transcriptome of H. alvei H4 wild-type at high cell density (OD600 = 1.7) relative to low cell density (OD600 = 0.3) was considered as growth phase-dependent manner (GPDM), and the transcriptome profile of luxI/R deletion mutant (ΔluxIR) compared to the wild-type was considered as QS-mediated regulation. In all, we identified 206 differentially expressed genes (DEGs) mainly presented in chemotaxis, TCA cycle, two-component system, ABC transporters and pyruvate metabolism, co-regulated by the both density-dependent regulation, and the results were validated by qPCR and swimming phenotypic assays. Aside from the co-regulated DEGs, we also found that 59 DEGs, mediated by density-independent QS, function in pentose phosphate and histidine metabolism and that 2084 cell-density-dependent DEGs involved in glycolysis/gluconeogenesis and phenylalanine metabolism were influenced only by GPDM from significantly enriched analysis of transcriptome data. The findings provided new information about the interplay between two density-dependent metabolic regulation, which could assist with the formulation of control strategies for this opportunistic pathogen, especially at high cell density.
Nitrogen Deposition Reduces the Diversity and Abundance of cbbL Gene-Containing CO2-Fixing Microorganisms in the Soil of the Stipa baicalensis Steppe
Authors: Qin Jie , Li Ming , Zhang Haifang , Liu Hongmei , Zhao Jianning , Yang Dianlin
Published: March 2021

CO2 fixation by autotrophic microbes has a significant effect on the carbon cycle in temperate grasslands. Nitrogen (N) deposition in soil has been steadily increasing for decades, which has consequences for soil microorganisms. However, the impact of this deposition on the diversity and abundance of CO2-fixing soil microorganisms remains unclear in temperate grasslands. In the present study, the cbbL gene, a key gene in the Calvin–Benson–Bassham cycle that encodes the large subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase, was used to study CO2-fixing microbes under different rates of N addition (0, 15, 30, 50, 100, and 150 kg N ha–1 yr–1) in a 9-year field experiment in a temperate grassland. The results showed that N addition led to significant reductions in cbbL gene abundance and genetic diversity and altered cbbL gene community composition. High N addition enhanced the relative abundances of Acidiferrobacterales and Rhizobiales but reduced those of Burkholderiales and Rhodobacterales. Structural equation modeling further revealed that N addition primarily reduced cbbL genetic diversity by increasing the soil NO3-N content and decreasing the soil pH. N addition indirectly reduced cbbL gene abundance, possibly by increasing the soil N/phosphorus (P) ratio and decreasing the soil pH. These findings suggest that N addition increases the soil available N and causes soil acidification, which may inhibit growth of CO2-fixing microbes to some extent.
A Machine Learning-Based Model to Predict Survival After Transarterial Chemoembolization for BCLC Stage B Hepatocellular Carcinoma
Authors: Lin Huapeng , Zeng Lingfeng , Yang Jing , Hu Wei , Zhu Ying
Published: March 2021

Objective

We sought to develop and validate a novel prognostic model for predicting survival of patients with Barcelona Clinic Liver Cancer Stages (BCLC) stage B hepatocellular carcinoma (HCC) using a machine learning approach based on random survival forests (RSF).

Methods

We retrospectively analyzed overall survival rates of patients with BCLC stage B HCC using a training (n = 602), internal validation (n = 301), and external validation (n = 343) groups. We extracted twenty-one clinical and biochemical parameters with established strategies for preprocessing, then adopted the RSF classifier for variable selection and model development. We evaluated model performance using the concordance index (c-index) and area under the receiver operator characteristic curves (AUROC).

Results

RSF revealed that five parameters, namely size of the tumor, BCLC-B sub-classification, AFP level, ALB level, and number of lesions, were strong predictors of survival. These were thereafter used for model development. The established model had a c-index of 0.69, whereas AUROC for predicting survival outcomes of the first three years reached 0.72, 0.71, and 0.73, respectively. Additionally, the model had better performance relative to other eight Cox proportional-hazards models, and excellent performance in the subgroup of BCLC-B sub-classification B I and B II stages.

Conclusion

The RSF-based model, established herein, can effectively predict survival of patients with BCLC stage B HCC, with better performance than previous Cox proportional hazards models.
A Nomogram Based on a Multiparametric Ultrasound Radiomics Model for Discrimination Between Malignant and Benign Prostate Lesions
Authors: Liang Lei , Zhi Xin , Sun Ya , Li Huarong , Wang Jiajun , Xu Jingxu , Guo Jun
Published: March 2021

Objectives

To evaluate the potential of a clinical-based model, a multiparametric ultrasound-based radiomics model, and a clinical-radiomics combined model for predicting prostate cancer (PCa).

Methods

A total of 112 patients with prostate lesions were included in this retrospective study. Among them, 58 patients had no prostate cancer detected by biopsy and 54 patients had prostate cancer. Clinical risk factors related to PCa (age, prostate volume, serum PSA, etc.) were collected in all patients. Prior to surgery, patients received transrectal ultrasound (TRUS), shear-wave elastography (SWE) and TRUS-guided prostate biopsy. We used the five-fold cross-validation method to verify the results of training and validation sets of different models. The images were manually delineated and registered. All modes of ultrasound radiomics were retrieved. Machine learning used the pathology of “12+X” biopsy as a reference to draw the benign and malignant regions of interest (ROI) through the application of LASSO regression. Three models were developed to predict the PCa: a clinical model, a multiparametric ultrasound-based radiomics model and a clinical-radiomics combined model. The diagnostic performance and clinical net benefit of each model were compared by receiver operating characteristic curve (ROC) analysis and decision curve.

Results

The multiparametric ultrasound radiomics reached area under the curve (AUC) of 0.85 for predicting PCa, meanwhile, AUC of B-mode radiomics and SWE radiomics were 0.74 and 0.80, respectively. Additionally, the clinical-radiomics combined model (AUC: 0.90) achieved greater predictive efficacy than the radiomics model (AUC: 0.85) and clinical model (AUC: 0.84). The decision curve analysis also showed that the combined model had higher net benefits in a wide range of high risk threshold than either the radiomics model or the clinical model.

Conclusions

Clinical-radiomics combined model can improve the accuracy of PCa predictions both in terms of diagnostic performance and clinical net benefit, compared with evaluating only clinical risk factors or radiomics score associated with PCa.
Risk of Recurrent Coronary Events in Patients With Familial Hypercholesterolemia; A 10-Years Prospective Study
Authors: Arnesen Kjell-Erik , Phung Ann Vinh , Randsborg Karoline , Mork Irene , Thorvall Marlene , Langslet Gisle , Svilaas Arne , Wium Cecilie , Ose Leiv , Retterstøl Kjetil
Published: March 2021

Background and Aim: Real world evidence on long term treatment of patients with familial hypercholesterolemia (FH) is important. We studied the effects of intensive lipid lowering medication (LLM) and optimized lifestyle in the study TTTFH–Treat To Target FH.

Materials and Methods: Adults with a first known total cholesterol of mean (95% CI) 9.8 mmol/L (9.5, 10.1) were included consecutively in their routine consultation during 2006. Of the patients 86.4% had a pathogenic FH-mutation and the remaining were clinically diagnosed. We included 357 patients and 279 met for follow-up after median 10.0 (min 8.1, max 12.8) years.

Results: Mean (95% CI) low density lipoprotein (LDL-C) was reduced from 3.9 (3.8, 4.1) to 3.0 (2.9, 3.2). More men than women used high intensity statin treatment, 85.2 and 60.8%, respectively. Women (n = 129) had higher LDL-C; 3.3 mmol/L (3.0, 3.5), than men; (n = 144) 2.8 mmol/L (2.6, 3.0), p = 0.004. Add-on PCSK9 inhibitors (n = 25) reduced mean LDL-C to 2.0 (1.4, 2.6) mmol/L. At enrollment 57 patients (20.4%) had established atherosclerotic cardiovascular disease (ASCVD), and 46 (80.4%) of them experienced a new event during the study period. Similarly, 222 (79.6%) patients had no detectable ASCVD at enrollment, and 29 of them (13.1%) experienced a first-time event during the study period.

Conclusion: A mean LDL-C of 3.0 mmol/L was achievable in FH, treated intensively at a specialized clinic with few users of PCSK9 inhibitors. LDL-C was higher (0.5 mmol/L) in women than in men. In patients with ASCVD at enrollment, most (80.7%) experienced a new ASCVD event in the study period. The FH patients in primary prevention had more moderate CV risk, 13% in ten years.
Indian Medicinal Plants and Formulations and Their Potential Against COVID-19–Preclinical and Clinical Research
Authors: Ahmad Sayeed , Zahiruddin Sultan , Parveen Bushra , Basist Parakh , Parveen Abida , Gaurav  , Parveen Rabea , Ahmad Minhaj
Published: March 2021

The cases of COVID-19 are still increasing day-by-day worldwide, even after a year of its first occurrence in Wuhan city of China. The spreading of SARS-CoV-2 infection is very fast and different from other SARS-CoV infections possibly due to structural differences in S proteins. The patients with severe diseases may die due to acute respiratory distress syndrome (ARDS) caused by systemic inflammatory reactions due to the excessive release of pro-inflammatory cytokines and chemokines by the immune effector cells. In India too, it is spreading very rapidly, although the case fatality rate is below 1.50% (https://www.statista.com), which is markedly less than in other countries, despite the dense population and minimal health infrastructure in rural areas. This may be due to the routine use of many immunomodulator medicinal plants and traditional AYUSH formulations by the Indian people. This communication reviews the AYUSH recommended formulations and their ingredients, routinely used medicinal plants and formulations by Indian population as well as other promising Indian medicinal plants, which can be tested against COVID-19. Special emphasis is placed on Indian medicinal plants reported for antiviral, immunomodulatory and anti-allergic/anti-inflammatory activities and they are categorized for prioritization in research on the basis of earlier reports. The traditional AYUSH medicines currently under clinical trials against COVID-19 are also discussed as well as furtherance of pre-clinical and clinical testing of the potential traditional medicines against COVID-19 and SARS-CoV-2. The results of the clinical studies on AYUSH drugs will guide the policymakers from the AYUSH systems of medicines to maneuver their policies for public health, provide information to the global scientific community and could form a platform for collaborative studies at national and global levels. It is thereby suggested that promising AYUSH formulations and Indian medicinal plants must be investigated on a priority basis to solve the current crisis.
Deficiency in Neuroserpin Exacerbates CoCl2 Induced Hypoxic Injury in the Zebrafish Model by Increased Oxidative Stress
Authors: Han Sha , Zhang Dongyang , Dong Qiang , Wang Xu , Wang Liang
Published: March 2021

Protective strategy against hypoxic-ischemic (H/I) induced injury has been intensively discussed. Neuroserpin, an inhibitor for tissue plasminogen activator (tPA), has been proved a vital neuroprotective agent in cerebral ischemia mouse model and oxygen-glucose deprivation and reoxygenation (OGD/R) cell model. Neuroserpin is a promising therapeutic hint for neonatal hypoxic-ischemia injury. Here, we established a neuroserpin deficient zebrafish to study its role in CoCl2 chemically induced hypoxic injury. CoCl2 exposure was beginning at the embryonic stage. Development defects, neuronal loss, and vascular malformation was assessed by imaging microscopy. Neuroserpin deficient zebrafish showed more development defects, neuronal loss and vascular malformation compared to wide-type. Apoptosis and oxidative stress were evaluated to further identify the possible mechanisms. These findings indicate that neuroserpin could protective against CoCl2 induced hypoxic injury by alleviating oxidative stress.
Plasma Levels of Neuron- and Astrocyte-Derived Exosomal Amyloid Beta1-42, Amyloid Beta1-40, and Phosphorylated Tau Levels in Schizophrenia Patients and Non-psychiatric Comparison Subjects: Relationships With Cognitive Functioning and Psychopathology
Authors: Lee Ellen E. , Winston-Gray Charisse , Barlow James W. , Rissman Robert A. , Jeste Dilip V.
Published: March 2021

Introduction: Cognitive deficits in people with schizophrenia (PWS) are a major predictor of disability and functioning, yet the underlying pathophysiology remains unclear. A possible role of amyloid and tau biomarkers (hallmarks of Alzheimer's disease) is still speculative in schizophrenia. Exosomes or extracellular vesicles, involved with cell-to-cell communication and waste removal, can be used to assay brain-based proteins from peripheral blood. To our knowledge, this is the first study of exosomal amyloid and tau protein levels in PWS.

Methods: This cross-sectional study included 60 PWS and 60 age- and sex-comparable non-psychiatric comparison subjects (NCs), age range 26–65 years. Assessments of global cognitive screening, executive functioning, psychopathology, and physical measures were conducted. Exosomes were extracted and precipitated from fasting plasma and identified as neuron-derived exosomes (NDEs) or astrocyte-derived exosomes (ADEs). Human-specific ELISAs were used to assay levels of amyloid-beta 1-42 (Aβ42), amyloid-beta 1-40 (Aβ40), and phosphorylated T181 tau (P-T181-tau). Plasma assays for aging biomarkers (C-reactive protein and F2-isoprostanes) were also performed.

Results: ADE-Aβ42 levels were higher in PWS compared to NCs, though the other exosomal markers were similar between the two groups. Higher ADE-P-T181-tau levels were associated with worse executive functioning. Among PWS, higher ADE-P-T181-tau levels were associated with less severe negative symptoms and increased F2-isoprostane levels. Astrocyte-derived Aβ marker levels were sensitive and specific in differentiating between diagnostic groups. Among PWS, Aβ40 levels differed most by exosomal origin.

Discussion: Exosomal markers may provide novel insights into brain-based processes (e.g., aging, oxidative stress) from peripheral blood samples.