bluuebunny/crossref_metadata_2025 huggingface dataset:
Growth and yield of maize (Zea mays L.) as influenced by date of sowing and hybrids
Authors: Sab Dadapeer Belaghatta Hassan , Sridhara Shankarappa , Gopakkali Pradeep
Published: January 2021

A field experiment was conducted at college of Agriculture, UAHS, Shivamogga during kharif 2015 to study the effect of date of sowing and hybrids on growth and yield of Maize (Zea maysL.). The experi-ment was laid out in randomized complete block design (RCBD) with factorial concept and replicated thrice. There were eight treatment combinations which includes four dates of sowing (15thJune, 30thJune, 15thJuly and 30thJuly) and two hybrids (PAC-740 and CP-818). Crop sown on 15thJune recorded significantly higher plant height (201.03 cm), number of green leaves (3.03), leaf area (992.49 cm2), LAI (0.74), total dry matter (305.65 g), cob length (22.16 cm), kernels cob-1 (670.93), kernel yield cob-1(230.95 g), test weight (43.08 g), kernel yield (7632.57 kg ha-1), stover yield (9512.56 kg ha-1) andhar-vest index (44.52 %)as compared to other sowing dates. Among the hybrids CP -818 recorded significantly higher plant height (191.85 cm), number of green leaves (2.72), leaf area (954.32 cm2), LAI (0.71), total dry matter (277.65 g), cob length (19.81 cm), kernels cob-1 (541.88), kernel yield cob-1(207.71 g), test weight (39.16 g), kernel yield (7060.72 kg ha-1), Stover yield (8839.98 kg ha-1) and harvest in-dex (44.44%) as compared to PAC-740. The interaction between dates of sowing and hybrids are non-significant.
vozes emudecidas
Authors: Braga Adriana de Carvalho Alves , Moura Christian Fernando dos Santos
Published: January 2021

En este artículo partimos de la concepción de la historia elaborada por Walter Benjamin, para meditar sobre el espacio que ocupan los sujetos subordinados en la producción historiográfica de América Latina. Con el fin de recuperar las voces silenciadas, en la construcción de la narrativa histórica de la región, analizamos la relevancia histórica de los códices, la posición privilegiada de Poma de Ayala en el registro de la colonización y las interpretaciones de Mariátegui. Utilizamos el marco explicativo de Edmundo O'Gorman para comprender cómo se inventó e incluyó la noción política de América en la concepción geoeconómica del sistema mundial. En estas reflexiones, centrarse en estos registros cumple el rol de cuestionar una perspectiva histórica relacionada con la “historia de los vencedores”, tendencia criticada por Walter Benjamin, y que opera en el sentido de invisibilizar las identidades sociales subalternizadas. Romper con la lógica colonial pasa por incorporar nuevas representaciones y formas de pensar el contexto vivido dentro de la situación colonial. Estos son elementos que contribuyen al giro decolonial, replanteando la memoria histórica latinoamericana.
cinema de Sara Gómez
Authors: Silva Cleonice Elias da
Published: January 2021

Este artigo apresenta aspectos do cinema da cineasta cubana Sara Gómez a partir da análise de alguns dos elementos presentes em seu único longa-metragem De cierta manera (1974). O filme subsidia discussões sobre a sociedade cubana no período pós-revolução de 1959, os problemas sociais, os conflitos e dicotomias existentes entre antigos valores e tradições diante do processo de transformação em curso. Apesar de considerar a leitura de que o filme apresenta uma discussão sobre o papel da mulher na sociedade cubana dos anos 1970, proponho uma reflexão sobre a questão da crise das identidades perante o processo modernizador.
IIRSA, Cosiplan e a atuação brasileira na consolidação da integração de infraestrutura na América do Sul
Authors: Grassi Jéssica Maria , Morais Silva Ana Karolina , Oliveira Lucas Kerr de
Published: January 2021

No presente artigo visamos discutir a atuação brasileira nos projetos da IIRSA e do Cosiplan, considerando as diferentes interpretações acerca do papel que o Brasil desempenhou neste processo. Inicialmente, são desenvolvidos os conceitos de subimperialismo, liderança regional e potência regional e, a partir desta discussão teórica-conceitual, o artigo explora a formação e evolução da IIRSA e do Cosiplan apresentando a atuação brasileira em ambos. Através desta revisão bibliográfica, combinada com a análise dos dados do investimento realizado nas iniciativas de integração de infraestrutura no mesmo período, buscamos testar a hipótese segundo a qual a participação brasileira na integração de infraestrutura sul-americana, durante os governos de Fernando Henrique Cardoso, Luiz Inácio Lula da Silva e Dilma Rousseff, se deu sob uma lógica subimperialista. Conclui-se que a tese do subimperialismo brasileiro não se sustenta através da revisão bibliográfica e dos dados de investimentos, os quais demonstram que o Brasil buscou liderar o processo de integração na região em uma ação coerente com os seus interesses geopolíticos, visando melhorar sua inserção internacional através da cooperação e da consolidação da integração do bloco regional sul-americano.
Cooperação e trânsito entre as ditaduras argentina e brasileira
Authors: Kosiak Ana Carolina , Gonçalves Marcos
Published: January 2021

Resumo: O artigo objetiva analisar os registros dos órgãos de segurança sobre as pessoas refugiadas argentinas que fugiam em direção a seu exílio no Brasil durante o período que compreende os anos de 1977 e 1979. A pesquisa utiliza como fonte o material produzido pelo grupo de trabalho formado durante a ditadura militar brasileira pelos ministérios das Relações Exteriores e da Justiça, órgãos de informação das forças armadas (CIE, CENIMAR, CISA); e informes do ACNUR que definiam possíveis países de acolhimento para exílio. Analisa-se a documentação como parte constituinte dos “arquivos da repressão”. Abordam-se as redes de cooperação e trânsito entre as ditaduras como responsáveis pela forma de tratamento aos refugiados, e depois exilados, vindos de sociedades que enfrentavam governos ditatoriais. Foram ações determinantes para a política de mobilidade forçada. Discute-se a política sobre a fronteira, apresentando a forma como ocorria o controle de pessoas que transitavam da Argentina para o Brasil, e a recusa de acolhimento de refugiados como uma prática governamental que refletia os interesses das ditaduras.
A Literatura Nazista na América (Roberto Bolaño)
Authors: Secco Lincoln
Published: January 2021

Literatura Nazista na América é um livro publicado em espanhol em 1996. Ele foi traduzido no Brasil em 2019.  São 31 estórias em 13 partes e um epílogo. Esta resenha discute o uso que o autor faz dos gêneros literários (conto, novela, relatos jornalísticos etc) e a combinação de personagens fictícios e reais.
Radiation Impacts Early Atherosclerosis by Suppressing Intimal LDL Accumulation
Authors: Ikeda Jiro , Scipione Corey A. , Hyduk Sharon J. , Althagafi Marwan G. , Atif Jawairia , Dick Sarah A. , Rajora Maneesha , Jang Erika , Emoto Takuo , Murakami Junichi , Ikeda Noriko , Ibrahim Hisham M. , Polenz Chanele K. , Gao Xiaotang , Tai Kelly , Jongstra-Bilen Jenny , Nakashima Ryota , Epelman Slava , Robbins Clinton S. , Zheng Gang , Lee Warren L. , MacParland Sonya A. , Cybulsky Myron I.
Published: January 2021

Rationale:

Bone marrow transplantation (BMT) is used frequently to study the role of hematopoietic cells in atherosclerosis, but aortic arch lesions are smaller in mice after BMT.

Objective:

To identify the earliest stage of atherosclerosis inhibited by BMT and elucidate potential mechanisms.

Methods and Results:

Ldlr
−/−
mice underwent total body γ-irradiation, bone marrow reconstitution, and 6-week recovery. Atherosclerosis was studied in the ascending aortic arch and compared with mice without BMT. In BMT mice, neutral lipid and myeloid cell topography were lower in lesions after feeding a cholesterol-rich diet for 3, 6, and 12 weeks. Lesion coalescence and height were suppressed dramatically in mice post-BMT, whereas lateral growth was inhibited minimally. Targeted radiation to the upper thorax alone reproduced the BMT phenotype. Classical monocyte recruitment, intimal myeloid cell proliferation, and apoptosis did not account for the post-BMT phenotype. Neutral lipid accumulation was reduced in 5-day lesions, thus we developed quantitative assays for LDL (low-density lipoprotein) accumulation and paracellular leakage using DiI-labeled human LDL and rhodamine B-labeled 70 kD dextran. LDL accumulation was dramatically higher in the intima of
Ldlr
−/−
relative to
Ldlr
+/+
mice, and was inhibited by injection of HDL mimics, suggesting a regulated process. LDL, but not dextran, accumulation was lower in mice post-BMT both at baseline and in 5-day lesions. Since the transcript abundance of molecules implicated in LDL transcytosis was not significantly different in the post-BMT intima, transcriptomics from whole aortic arch intima, and at single-cell resolution, was performed to give insights into pathways modulated by BMT.

Conclusions:

Radiation exposure inhibits LDL entry into the aortic intima at baseline and the earliest stages of atherosclerosis. Single-cell transcriptomic analysis suggests that LDL uptake by endothelial cells is diverted to lysosomal degradation and reverse cholesterol transport pathways. This reduces intimal accumulation of lipid and impacts lesion initiation and growth.
Canagliflozin Suppresses Atrial Remodeling in a Canine Atrial Fibrillation Model
Authors: Nishinarita Ryo , Niwano Shinichi , Niwano Hiroe , Nakamura Hironori , Saito Daiki , Sato Tetsuro , Matsuura Gen , Arakawa Yuki , Kobayashi Shuhei , Shirakawa Yuki , Horiguchi Ai , Ishizue Naruya , Igarashi Tazuru , Yoshizawa Tomoharu , Oikawa Jun , Hara Yoshinobu , Katsumura Takafumi , Kishihara Jun , Satoh Akira , Fukaya Hidehira , Sakagami Hiroyuki , Ako Junya
Published: January 2021

Background

Recent clinical trials have demonstrated the possible pleiotropic effects of SGLT2 (sodium–glucose cotransporter 2) inhibitors in clinical cardiovascular diseases. Atrial electrical and structural remodeling is important as an atrial fibrillation (AF) substrate.

Methods and Results

The present study assessed the effect of canagliflozin (CAN), an SGLT2 inhibitor, on atrial remodeling in a canine AF model. The study included 12 beagle dogs, with 10 receiving continuous rapid atrial pacing and 2 acting as the nonpacing group. The 10 dogs that received continuous rapid atrial pacing for 3 weeks were subdivided as follows: pacing control group (n=5) and pacing+CAN (3 mg/kg per day) group (n=5). The atrial effective refractory period, conduction velocity, and AF inducibility were evaluated weekly through atrial epicardial wires. After the protocol, atrial tissues were sampled for histological examination. The degree of reactive oxygen species expression was evaluated by dihydroethidium staining. The atrial effective refractory period reduction was smaller (
P
=0.06) and the degree of conduction velocity decrease was smaller in the pacing+CAN group compared with the pacing control group (
P
=0.009). The AF inducibility gradually increased in the pacing control group, but such an increase was suppressed in the pacing+CAN group (
P
=0.011). The pacing control group exhibited interstitial fibrosis and enhanced oxidative stress, which were suppressed in the pacing+CAN group.

Conclusions

CAN and possibly other SGLT2 inhibitors might be useful for preventing AF and suppressing the promotion of atrial remodeling as an AF substrate.
Some Endangered Feeling
Authors: Armstrong Nancy
Published: January 2021

This essay sees the recent trend in novels that feature damaged, partial, or wayward protagonists as the ascent of a tradition of formal outliers as old as the novel itself to a position of dominance. Rather than formulate a self-contained individual capable of defending itself against whatever forces of nature or society might disperse and refigure it, this other tradition gave into those forces, releasing human subjectivity from the confines of the self-regulating individual. Why now? How does this major turn in the history of the novel contribute to the current reconsideration of human motivation and behavior in light of affect theory? If Robinson Crusoe provided a bellwether for the individual to come, then what can the damaged protagonist of Tom McCarthy's 2005 novel Remainder tell us about the selves we are likely to become?
Whence the Expected Free Energy?
Authors: Millidge Beren , Tschantz Alexander , Buckley Christopher L.
Published: January 2021

The expected free energy (EFE) is a central quantity in the theory of active inference. It is the quantity that all active inference agents are mandated to minimize through action, and its decomposition into extrinsic and intrinsic value terms is key to the balance of exploration and exploitation that active inference agents evince. Despite its importance, the mathematical origins of this quantity and its relation to the variational free energy (VFE) remain unclear. In this letter, we investigate the origins of the EFE in detail and show that it is not simply ”the free energy in the future.” We present a functional that we argue is the natural extension of the VFE but actively discourages exploratory behavior, thus demonstrating that exploration does not directly follow from free energy minimization into the future. We then develop a novel objective, the free energy of the expected future (FEEF), which possesses both the epistemic component of the EFE and an intuitive mathematical grounding as the divergence between predicted and desired futures.
Near Eastern Echoes in Iliad 16.33–35
Authors: Alepidou Apostolia
Published: January 2021

This article reexamines Patroclus’s famous comment on Achilles’s cruelty in which the sea and the rocks take up the role of the latter’s parents (Iliad 16.33–35). The verses reflect Near Eastern myths about the birth of menacing creatures from the sea and the rocks and are particularly associated with the Song of Hedammu and the Song of Ullikummi of the Hurro-Hittite tradition. Thematic, mythological, and dictional parallels among these texts are discussed in order to explore the existence of a common theme with specific connotations in the broader region of West Asia.
Gladiolus aladagensis (Iridaceae), a new species from Turkey

Authors: SAĞIROĞLU MEHMET , EKER İSMAİL
Published: January 2021

Gladiolus aladagensis is described and illustrated as a new species from Bolu province in Northwestern Anatolia, Turkey. Gladiolus aladagensis is morphologically close to G. italicus and G. kotschyanus. In this study, the diagnostic morphological features, distribution, conservation status, habitat and ecological characteristics of the new species are discussed. Micromorphological characteristics of G. aladagensis, G. italicus and G. kotschyanus seeds are also examined and compared using LM and SEM analyses. In addition, a new diagnostic key is given for all species of Gladiolus in Turkey.
The Turbulent Structure of the Marine Atmospheric Boundary Layer during and before a Cold Front
Authors: Huang Jian , Zou Zhongshui , Zeng Qingcun , Li Peiliang , Song Jinbao , Wu Lin , Zhang Jun A. , Li Shuiqing , Chan Pak-wai
Published: January 2021

The turbulent structure within the marine atmospheric boundary layer is investigated based on four levels of observations at a fixed marine platform. During and before a cold front, the ocean surface is dominated by wind sea and swell waves, respectively, affording the opportunity to test the theory recently proposed in laboratory experiments or for flat land surfaces. The results reveal that the velocity spectra follow a k−1 law within the intermediate wavenumber (k) range immediately below inertial subrange during the cold front. A logarithmic height dependence of the horizontal velocity variances is also observed above the height of 20 m, while the vertical velocity variances increase with increasing height following a power law of 2/3. These features confirm the attached eddy model and the “top-down model” of turbulence over the ocean surface. However, the behavior of velocity variances under swell conditions is much different from those during the cold front, although a remarkable k−1 law can be observed in the velocity spectra. The quadrant analysis of the momentum flux also shows a significantly different result for the two conditions.
Oil-soluble ionic liquid to lubricate silicon
Authors: Al-Sallami Waleed , Parsaeian Pourya , Dorgham Abdel , Neville Anne
Published: January 2021

Trihexyltetradecylphosphonium bis(2-ethylhexyl)phosphate (phosphonium phosphate) ionic liquid is soluble in non-polar lubricants. It has been proposed as an effective anti-wear additive comparable to zinc dialkyldithiophosphate. Previously, phosphonium phosphate has shown a better anti-wear performance under some conditions such as high temperature. In this work, the tribological performance and the lubrication mechanism of phosphonium phosphate are compared with that of zinc dialkyldithiophosphate when lubricating silicon under various tribological conditions. This can lead to an understanding of the reasons behind the superior anti-wear performance of phosphonium phosphate under some conditions. A micro-scale study is conducted using a nanotribometer. The results show that both additives lead to a considerable reduction in both friction and wear coefficients. The reduction in the wear coefficient is mainly controlled by the formation of the tribofilm on the rubbing surfaces. Zinc dialkyldithiophosphate can create a thicker tribofilm, which results in a better anti-wear performance. However, the formation of a thicker film will lead to a faster depletion and thus phosphonium phosphate can provide better anti-wear performance when the depletion of zinc dialkyldithiophosphate starts.
Research on the fluctuation of the velocity and pressure of the flow field of an aerostatic bearing with a multi-hole integrated restrictor
Authors: Lu Zhiwei , Zhang Junan , Liu Bo
Published: January 2021

For an aerostatic bearing with a multi-hole integrated restrictor, which achieved superior precision lubrication-bearing performance, the fluctuations of the velocity and the pressure of the flow field were investigated. In this paper, the large-eddy simulation method was used to solve the three-dimensional Navier–Stokes equation in the calculation area of the gas film flow field at the orifice outlet of an aerostatic bearing, while the overrelaxation iteration method was used to solve the Reynolds equation in the remaining calculation areas. The influence factors of the flow field, such as the diameter of the orifice, the gas supply pressure and the gas film clearance, were derived and discussed. The results showed that the diameter of the orifice and the gas film clearance of aerostatic bearings with a multi-hole integrated restrictor strongly affected the film flow field near the outlet of the restrictor under a specified gas supply pressure. There was a critical ratio between the gas film clearance and the diameter of the orifice of aerostatic bearings with a multi-hole integrated restrictor, which may be an initial signal and an important parameter of the flow field transition from laminar flow to turbulent flow.
Predictors of pediatric readmissions among patients with neurological conditions
Authors: O’Connell Ryan , Feaster William , Wang Vera , Taraman Sharief , Ehwerhemuepha Louis
Published: January 2021

Background

Unplanned readmission is one of many measures of the quality of care of pediatric patients with neurological conditions. In this multicenter study, we searched for novel risk factors of readmission of patients with neurological conditions.

Methods

We retrieved hospitalization data of patients less than 18 years with one or more neurological conditions. This resulted in a total of 105,834 encounters from 18 hospitals. We included data on patient demographics, prior healthcare resource utilization, neurological conditions, number of other conditions/diagnoses, number of medications, and number of surgical procedures performed. We developed a random intercept logistic regression model using stepwise minimization of Akaike Information Criteria for variable selection.

Results

The most important neurological conditions associated with unplanned pediatric readmissions include hydrocephalus, inflammatory diseases of the central nervous system, sleep disorders, disease of myoneural junction and muscle, other central nervous system disorder, other spinal cord conditions (such as vascular myelopathies, and cord compression), and nerve, nerve root and plexus disorders. Current and prior healthcare resource utilization variables, number of medications, other diagnoses, and certain inpatient surgical procedures were associated with changes in odds of readmission. The area under the receiver operator characteristic curve (AUROC) on the independent test set is 0.733 (0.722, 0.743).

Conclusions

Pediatric patients with certain neurological conditions are more likely to be readmitted than others. However, current and prior healthcare resource utilization remain some of the strongest indicators of readmission within this population as in the general pediatric population.
The Iranian version of theory-based intention for cesarean section (IR-TBICS) scale: development and first evaluation
Authors: Naghibi Seyed Abolhassan , Khazaee-Pool Maryam , Moosazadeh Mahmood
Published: January 2021

Background

The rate at which mothers experience a cesarean section in the absence of medical signs is growing worldwide. Women’s beliefs and intentions play an essential role in the request or choice of a delivery method. At present, there is no comprehensive, validated scale for assessing pregnant women’s beliefs about cesarean section in the Iranian population. This study was performed to develop and assess the validity and reliability of the intention-based cesarean section scale using the theory of reasoned action (TRA) constructs as a theoretical framework for measuring intention toward the selection of a delivery method.

Methods

In this cross-sectional validation study, 480 pregnant women were recruited from Sari, in northern Iran, through a multistage random sampling approach. Content validity was examined using the content validity index (CVI) and content validity ratio (CVR). Furthermore, both exploratory factor analyses (EFA) and confirmatory factor analyses (CFA) were applied to assess the construct validity of the developed scale. Reliability was measured by internal consistency and the intraclass correlation coefficient (ICC). Quality criteria for floor and ceiling effects were derived from existing guidelines and consensus within our research group.

Results

The results obtained from the factor analysis showed that the data were fit to the model (χ2 = 2298.389, P < 0.001). The TRA comprised 24 items assessing five domains, which described 62.46% of the common variance. The CFA showed a model with suitable fitness for the data. Cronbach’s alpha coefficient for the domains of the scale ranged from 0.609 to 0.843, and the ICC value ranged from 0.71 to 0.84, which is within the satisfactory range. The IR-TBICS scale had no floor or ceiling effect on the total score or any of the dimensions.

Conclusions

The belief-based cesarean section scale appears to be a reliable instrument. It is considered suitable and can be applied in other research in Iran.
CA724 predicts overall survival in locally advanced gastric cancer patients with neoadjuvant chemotherapy
Authors: Tong Yilin , Zhao Yan , Shan Zexing , Zhang Jianjun
Published: January 2021

Background

Serum tumor markers including AFU, AFP, CEA, CA199, CA125 and CA724, are of great importance in the diagnosis, prognostic prediction and recurrence monitoring of gastrointestinal malignancies. However, their significance in gastric cancer (GC) patients with neoadjuvant therapy (NCT) is still uncertain. The aim of this study was to evaluate the predictive value of these six tumor markers in locally advanced GC patients who underwent NCT and curative surgery.

Methods

In total, 290 locally advanced GC patients who underwent NCT and D2 radical gastrectomy were retrospectively analyzed. Data on their tumor markers before (pre-) and after (post-) NCT and pathological characteristics were extracted from the database of our hospital. The optimal cutoff values of the six tumor markers were calculated by the ROC curve and Youden index. Their predictive significance was analyzed and survival curves for overall survival (OS) were obtained by the Kaplan-Meier method. Associations between categorical variables were explored by the chi-square test or Fisher’s exact test. Multivariate analyses were performed by the Cox regression model.

Results

Pre- and post-CA199, −CA125 and -CA724 could predict overall survival (all P < 0.05), but only the change (diff-) of CA199 was related to prognosis (P = 0.05). In the multivariable analysis, pre- (P = 0.014) and post-CA724 (P = 0.036) remained significant, though diff-CA724 was not an independent prognostic factor (P = 0.581). In addition, pre- and post-CA199, −CA125 and -CA724 were associated with lymph node metastasis (N- vs N+) and pathological stage (I-II vs III) (all P < 0.05). Moreover, post-CA724 was related to the vascular or lymphatic invasion (P = 0.019), while pre-CA724 was not (P = 0.082). However, AFU, AFP and CEA showed no association with survival (P > 0.05).

Conclusions

CA724 is an independent factor for prognosis and could be used to predict ypN and ypTNM stage in locally advanced GC patients undergoing NCT and curative resection.
A gene-based risk score model for predicting recurrence-free survival in patients with hepatocellular carcinoma
Authors: Wang Wenhua , Wang Lingchen , Xie Xinsheng , Yan Yehong , Li Yue , Lu Quqin
Published: January 2021

Background

Hepatocellular carcinoma (HCC) remains the most frequent liver cancer, accounting for approximately 90% of primary liver cancers worldwide. The recurrence-free survival (RFS) of HCC patients is a critical factor in devising a personal treatment plan. Thus, it is necessary to accurately forecast the prognosis of HCC patients in clinical practice.

Methods

Using The Cancer Genome Atlas (TCGA) dataset, we identified genes associated with RFS. A robust likelihood-based survival modeling approach was used to select the best genes for the prognostic model. Then, the GSE76427 dataset was used to evaluate the prognostic model’s effectiveness.

Results

We identified 1331 differentially expressed genes associated with RFS. Seven of these genes were selected to generate the prognostic model. The validation in both the TCGA cohort and GEO cohort demonstrated that the 7-gene prognostic model can predict the RFS of HCC patients. Meanwhile, the results of the multivariate Cox regression analysis showed that the 7-gene risk score model could function as an independent prognostic factor. In addition, according to the time-dependent ROC curve, the 7-gene risk score model performed better in predicting the RFS of the training set and the external validation dataset than the classical TNM staging and BCLC. Furthermore, these seven genes were found to be related to the occurrence and development of liver cancer by exploring three other databases.

Conclusion

Our study identified a seven-gene signature for HCC RFS prediction that can be used as a novel and convenient prognostic tool. These seven genes might be potential target genes for metabolic therapy and the treatment of HCC.
Lutetium oxodotreotide (177Lu-Dotatate) for the treatment of unresectable or metastatic progressive gastroenteropancreatic neuroendocrine tumors: a cost-effectiveness analysis for Scotland
Authors: Smith-Palmer J. , Leeuwenkamp O. R. , Virk J. , Reed N.
Published: January 2021

Background

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) represent a heterogenous group of tumors. Findings from the phase III NETTER-1 trial showed that treatment of unresectable/metastatic progressive gastrointestinal (GI) NETs with 177Lu-Dotatate resulted in a significant improvement in progression-free survival (PFS) and overall survival (OS) compared with best supportive care (BSC) with high dose octreotide long-acting repeatable (LAR) 60 mg. A health economic analysis was performed using input data from clinical studies and data derived from an indirect comparison to determine the cost-effectiveness of 177Lu-Dotatate in the treatment of GI-NETs and pancreatic NETs (P-NETs) in Scotland.

Methods

Cost-effectiveness analysis was performed from the payer perspective using a three-state partitioned survival model. In the base case 177Lu-Dotatate was compared with BSC in gastrointestinal (GI)-NETs using clinical data from the NETTER-1 trial. A secondary analysis comparing 177Lu-Dotatate with BSC, everolimus or sunitinib in patients with P-NETs was also performed using hazard ratios inferred from indirect comparisons. The base case analysis was performed over a 20-year time horizon with an annual discount rate of 3.5% for both costs and clinical outcomes.

Results

For unresectable/metastatic progressive GI-NETs treatment with 177Lu-Dotatate led to a gain in quality-adjusted life expectancy of 1.33 quality-adjusted life years (QALYs) compared with BSC due to extended PFS and OS. Mean total lifetime costs were GBP 35,701 higher with 177Lu-Dotatate, leading to an incremental cost-effectiveness ratio (ICER) of GBP 26,830 per QALY gained.

In analyses in patients with P-NETs 177Lu-Dotatate was associated with ICERs below GBP 30,000 per QALY gained in comparisons with BSC, sunitinib and everolimus.

Conclusions

Cost-effectiveness analyses demonstrated that, in Scotland, from the payer perspective, 177Lu-Dotatate at the set acquisition cost is a cost-effective treatment option for patients with unresectable or metastatic progressive GI-NETs or P-NETs.
Translational control of Bcl-2 promotes apoptosis of gastric carcinoma cells
Authors: Tao Shuangfen , Gu Jianchun , Wang Qing , Zheng Leizhen
Published: January 2021

Background

Anti-apoptotic protein Bcl-2 plays a substantial role in the carcinogenesis, whereas the regulation for Bcl-2 in gastric carcinoma (GC) is poorly understood. Specifically, a role of microRNA (miR)-383 in the control of Bcl-2 has not been shown in GC and thus addressed in the current study.

Methods

We investigated the levels of miR-383 and Bcl-2 in 50 GC specimens, and compared them with patients’ clinical characteristics. Bioinformatics analyses and luciferase-reporter assay were applied for analyzing the relationship between Bcl-2 and miR-383. An CCK assay was used to determine the survival of Fluorouracil-treated GC cells, and apoptosis of GC cells was assessed by flow cytometric FITC Annexin V apoptosis detection assay and expression of apoptosis-associated proteins.

Results

The levels of miR-383 were lower while the levels of Bcl-2 levels were higher in GC specimens, compared to tissue from the adjacent non-tumor region. Low miR-383 and high Bcl-2 seemed to be associated with high malignancy and metastasis. In GC specimens, the levels of Bcl-2 and miR-383 inversely correlated. The overall survival of miR-383-low cases was poorer. Mechanistically, miR-383 targeted the 3′-UTR of Bcl-2 mRNA to inhibit its protein translation. Overexpression of miR-383 downregulated Bcl-2, resulting in reduced survival of Fluorouracil-treated GC cells. Similar conclusion was drawn through analysis of published database.

Conclusion

MiR-383 reduces survival of Fluorouracil-treated GC cells through downregulating of Bcl-2.
Characteristics and outcomes of patients with RET-fusion positive non-small lung cancer in real-world practice in the United States
Authors: Hess Lisa M. , Han Yimei , Zhu Yajun Emily , Bhandari Naleen Raj , Sireci Anthony
Published: January 2021

Background

Contradictory and limited data are available about the presentation and outcomes of patients with RET-fusion positive metastatic NSCLC as compared to patients without RET fusions. This observational study utilizing a linked electronic health records (EHR) database to genomics testing results was designed to compare characteristics, tumor response, progression-free (PFS) and overall survival (OS) outcomes by RET fusion status among patients with metastatic NSCLC treated with standard therapies.

Methods

Adult patients with metastatic NSCLC with linked EHR and genomics data were eligible who received systemic anti-cancer therapy on or after January 1, 2011. Adjusted, using all available baseline covariates, and unadjusted analyses were conducted to compare tumor response, PFS and OS between patients with RET-fusion positive and RET-fusion negative disease as detected by next-generation sequencing. Tumor response outcomes were analysed using Fisher’s exact test, and time-to-event analyses were conducted using Cox proportional hazards model.

Results

There were 5807 eligible patients identified (RET+ cohort, N = 46; RET- cohort, N = 5761). Patients with RET fusions were younger, more likely to have non-squamous disease and be non-smokers and had better performance status (all p < 0.01). In unadjusted analyses, there were no significant differences in tumor response (p = 0.17) or PFS (p = 0.06) but OS was significantly different by RET status (hazard ratio, HR = 1.91, 95% CI:1.22–3.0, p = 0.005). There were no statistically significant differences by RET fusion status in adjusted analyses of either PFS or OS (PFS HR = 1.24, 95% CI:0.86–1.78, p = 0.25; OS HR = 1.52, 95% CI: 0.95–2.43, p = 0.08).

Conclusions

Patients with RET fusions have different baseline characteristics that contribute to favorable OS in unadjusted analysis. However, after adjusting for baseline covariates, there were no significant differences in either OS or PFS by RET status among patients treated with standard therapy prior to the availability of selective RET inhibitors.
Competing risk analysis of cardiovascular/cerebrovascular death in T1/2 kidney cancer: a SEER database analysis
Authors: Mo Xiaofei , Zhou Mingge , Yan Hui , Chen Xueqin , Wang Yuetao
Published: January 2021

Background

Kidney cancer (KC) is associated with cardiovascular regulation disorder and easily leads to cardiovascular and cerebrovascular death (CCD), which is one of the major causes of death in patients with KC, especially those with T1/2 status. However, few studies have treated CCD as an independent outcome for analysis. We aimed to identify and evaluate the key factors associated with CCD in patients with T1/2 KC by competing risk analysis and compared these risk factors with those associated with kidney cancer-specific death (KCD) to offer some information for clinical management.

Methods

A total of 45,117 patients diagnosed with first primary KC in T1/2 status were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. All patients were divided into the CCD group (n = 3087), KCD group (n = 3212), other events group (n = 6312) or alive group (n = 32,506). Patients’ characteristics were estimated for their association with CCD or KCD by a competing risk model. Pearson’s correlation coefficient and variance inflation factor (VIF) were used to detect collinearity between variables. Factors significantly correlated with CCD or KCD were used to create forest plots to compare their differences.

Results

The competing risk analysis showed that age at diagnosis, race, AJCC T/N status, radiation therapy, chemotherapy and scope of lymph node represented different relationships to CCD than to KCD. In detail, age at diagnosis (over 74/1–50: HR = 9.525, 95% CI: 8.049–11.273), race (white/black: HR = 1.475, 95% CI: 1.334–1.632), AJCC T status (T2/T1: HR = 0.847, 95% CI: 0.758–0.946) and chemotherapy (received/unreceived: HR = 0.574, 95% CI: 0.347–0.949) were correlated significantly with CCD; age at diagnosis (over 74/1–50: HR = 3.205, 95% CI: 2.814–3.650), AJCC T/N status (T2/T1: HR = 2.259, 95% CI: 2.081–2.451 and N1/N0:HR = 3.347, 95% CI: 2.698–4.152), radiation therapy (received/unreceived: HR = 2.552, 95% CI: 1.946–3.346), chemotherapy (received/unreceived: HR = 2.896, 95% CI: 2.342–3.581) and scope of lymph nodes (1–3 regional lymph nodes removed/none: HR = 1.378, 95% CI: 1.206–1.575) were correlated significantly with KCD.

Conclusions

We found that age at diagnosis, race, AJCC T status and chemotherapy as the independent risk factors associated with CCD were different from those associated with KCD.
A population-based analysis of spirometry use and the prevalence of chronic obstructive pulmonary disease in lung cancer
Authors: Corriveau Sophie , Pond Gregory R. , Tang Grace H. , Goffin John R.
Published: January 2021

Background

Chronic obstructive pulmonary disease (COPD) and lung cancer are associated diseases. COPD is underdiagnosed and thus undertreated, but there is limited data on COPD diagnosis in the setting of lung cancer. We assessed the diagnosis of COPD with lung cancer in a large public healthcare system.

Methods

Anonymous administrative data was acquired from ICES, which links demographics, hospital records, physician billing, and cancer registry data in Ontario, Canada. Individuals age 35 or older with COPD were identified through a validated, ICES-derived cohort and spirometry use was derived from physician billings. Statistical comparisons were made using Wilcoxon rank sum, Cochran-Armitage, and chi-square tests.

Results

From 2002 to 2014, 756,786 individuals were diagnosed with COPD, with a 2014 prevalence of 9.3%. Of these, 51.9% never underwent spirometry. During the same period, 105,304 individuals were diagnosed with lung cancer, among whom COPD was previously diagnosed in 34.9%. Having COPD prior to lung cancer was associated with lower income, a rural dwelling, a lower Charlson morbidity score, and less frequent stage IV disease (48 vs 54%, p < 0.001). Spirometry was more commonly undertaken in early stage disease (90.6% in stage I-II vs. 54.4% in stage III-IV).

Conclusion

Over a third of individuals with lung cancer had a prior diagnosis of COPD. Among individuals with advanced lung cancer, greater use of spirometry and diagnosis of COPD may help to mitigate respiratory symptoms.
Sorafenib as a second-line treatment in metastatic renal cell carcinoma in Mexico: a prospective cohort study
Authors: Martín-Aguilar Ana Elena , Núñez-López Haidé , Ramirez-Sandoval Juan C.
Published: January 2021

Background

Sequential inhibition of the vascular endothelial growth factor (VEGF) pathway with sorafenib could be useful for patients with metastatic renal cell carcinoma (RCC). Our aim was to determine the activity and tolerability of sorafenib as a second-line therapy in advanced RCC initially treated with a different VEGF-tyrosine kinase inhibitor (TKI).

Methods

A prospective observational cohort in Mexico (2012–2019). We included 132 subjects with metastatic RCC and who had progression despite treatment with sunitinib. The primary end-point was time to disease progression as evaluated every 12–16 weeks.

Results

The mean age of the cohort was 59 years (interquartile range [IQR] 50–72), 96 (73%) were men, and 48 (36%) had a favorable prognosis according to the IMDC (International Metastatic RCC Database Consortium) prognostic model. The median progression-free survival (PFS) and overall-survival after the introduction of sorafenib treatment was 8.6 months (95% confidence interval [CI]: 6.7–10.5) and 40 months (95% CI: 34.5–45.4) respectively. The median overall survival from RCC diagnosis to death was 71 months (95% CI: 58.2–83.8). On multivariable analyses, age > 65 years was associated with a longer PFS (HR 0.51; 95% CI: 0.31–0.86; p = 0.018). The median PFS in subjects aged > 65 years was longer compared to subjects ≤65 years (14.0 [95% CI: 9.2–18.8] vs. 7.2 months [95% CI: 5.3–9.1]; p = 0.012). Adverse events grade ≥ 3 associated with sorafenib occurred in 38 (29%) patients.

Conclusion

Sequential inhibition of VEGF with sorafenib as a second-line treatment may benefit patients with metastatic RCC, especially in subjects > 65 years old.
Low expression of ferritinophagy-related NCOA4 gene in relation to unfavorable outcome and defective immune cells infiltration in clear cell renal carcinoma
Authors: Mou Yanhua , Wu Jinchun , Zhang Yao , Abdihamid Omar , Duan Chaojun , Li Bin
Published: January 2021

Background

Clear cell renal cell carcinoma is susceptible to ferroptosis, and immunotherapy is recently recommended as a priority for the initial treatment of metastatic clear cell renal carcinoma. Increased ferroptosis and immune activation can synergistically reinforce each other in killing cancer cells. NCOA4 depletion can eliminate iron accumulation and thus weaken ferroptosis. Here, we aim to identify and validate the association between NCOA4 expression, clinicopathologic characteristics, and overall survival in ccRCC by using The Cancer Genome Atlas and Gene Expression Omnibus databases. We further analyze the interacted proteins of NCOA4 and infiltrated immune cells via TIMER and GEPIA databases.

Methods

NCOA4 expression in clear cell renal carcinoma (ccRCC) tissues and normal adjacent tissues in The Cancer Genome Atlas (TCGA) data were primarily screened, and further validated in another independent cohort from the gene expression omnibus (GEO) database and human protein atlas. The relationships of NCOA4 expression and clinicopathologic parameters and overall survival (OS) were assessed using multivariate methods and Kaplan-Meier survival curves. And the proteins network with which NCOA4 interacted were also built using the online STRING website. Meanwhile, we use TIMER and GEPIA databases to investigate the relationships between NCOA4 expression and infiltrated immune cells and their corresponding gene marker sets.

Results

Contrast to normal tissue, NCOA4 expression was lower in ccRCC tumor tissue(p < 0.05). Lower NCOA4 expression was closely associated with high-grade malignancy and advanced TNM stage. Univariate and multivariate analysis indicated the overall survival of ccRCC cases with low NCOA4 level is shorter than those of patients with high NCOA4 expression (p < 0.05). FTL and FTH1 were the important proteins interacting with NCOA4. ccRCC with NCOA4 deficiency presented the paucity of infiltrated immune cells and their matching marker sets, including CD8+ T cells.

Conclusion

Deficient NCOA4 expression was related to disease progression and poor prognosis, as well as impaired infiltration of immune cells in ccRCC.
Actual long-term survival after resection of stage III soft tissue sarcoma
Authors: Lee Do Weon , Kim Han-Soo , Han Ilkyu
Published: January 2021

Background

Actuarial survival based on the Kaplan–Meier method can overestimate actual long-term survival, especially among those with factors of poor prognosis. Patients with American Joint Committee on Cancer stage III soft tissue sarcoma (STS) represent a subset with a high risk of STS-specific mortality. Therefore, we aimed to characterize the clinicopathological characteristics associated with actual long-term survival in patients with stage III STS.

Methods

We retrospectively reviewed 116 patients who underwent surgical resection for stage III STS with curative intent between March 2000 and December 2013. Long-term survivors (n = 61), defined as those who survived beyond 5 years, were compared with short-term survivors (n = 36), who died of STS within 5 years.

Results

Multivariate logistic regression analyses showed that a tumor size < 10 cm [odds ratio (OR) 3.95,p = 0.047], histological grade of 2 (OR 8.12,p = 0.004), and American Society of Anesthesiologists (ASA) score of 1 (OR 11.25,p = 0.001) were independently associated with actual 5-year survival. However, 66% of the long-term survivors exhibited factors of poor prognosis: 36% had a tumor size > 10 cm and 48% had a histological grade of 3. Leiomyosarcoma (3 of 10) was negatively associated with actual long-term survival.

Conclusions

Actual 5-year survival after resection of stage III STS was associated with tumor size, histological grade, and ASA score. However, majority of the actual 5-year survivors exhibit factors of poor prognosis, suggesting that aggressive treatment should be offered for a chance of long-term survival in these patients.
IgG4-related disease presenting as recurrent scleritis combined with optic neuropathy
Authors: Kim Su Jin , Lee Seung Uk , Kang Min Seung , Ahn Jung Hyo , Shin Jonghoon , Park Choul Yong , Lee Ji Eun
Published: January 2021

Background

We report a case of atypical presentation of IgG4-related disease (IgG4-RD) with recurrent scleritis and optic nerve involvement.

Case presentation

A 61-year-old male presented with ocular pain and injection in his left eye for 2 months. Ocular examination together with ancillary testing led to the diagnosis of scleritis, which relapsed in spite of several courses of steroid treatment. After cessation of steroid, the patient complained of severe retro-orbital pain and blurred vision. His best corrected vision was count finger, the pupil was mid-dilated and a relative afferent pupillary defect was found. Funduscopic examination demonstrated disc swelling. Magnetic resonance imaging (MRI) showed enhancing soft tissue encasing the left globe, medial rectus muscle and optic nerve. Systemic work-up revealed multiple nodules in right lower lung and a biopsy showed histopathological characteristics of IgG4-RD. Long-term treatment with corticosteroids and a steroid-sparing agent (methotrexate) led to significant improvement in signs and symptoms with no recurrence for 2 years.

Conclusions

This case highlights the significance of IgG4-RD in the differential diagnosis of recurrent scleritis. IgG4-RD may cause optic neuropathy resulting in visual loss. Early diagnosis and proper treatment can prevent irreversible organ damage and devastating visual morbidity.
Psychometric properties of the Norwegian version of the Patient Health Questionnaire-9 (PHQ-9) in a large female sample of adults with and without eating disorders
Authors: Wisting Line , Johnson Sverre Urnes , Bulik Cynthia M. , Andreassen Ole A. , Rø Øyvind , Bang Lasse
Published: January 2021

Background

Internationally, the Patient Health Questionnaire-9 (PHQ-9) is commonly used to assess the frequency and severity of depressive symptoms. However, psychometric properties of the Norwegian version of the PHQ-9 have only been assessed in adolescents. We present normative data for women and an evaluation of the psychometric properties (internal consistency, convergent validity, and factor structure) of the Norwegian PHQ-9 among women with and without eating disorders (ED).

Methods

In this case-control study, a total of 793 females aged 18–78 years (mean 30.39; SD 9.83) completed an online self-report assessment. Measures included the ED100K and Eating Disorder Examination Questionnaire (EDE-Q) to assess ED psychopathology, and the Generalized Anxiety Disorder (GAD) scale and Difficulties in Emotion Regulation Scale Short Form (DERS-SF) to assess symptoms of anxiety and emotion regulation deficits. Participants were categorized into three groups, i.e., previous ED (19.7%, n = 148), current ED (36.3%, n = 272), and no history of ED (44.0%, n = 330), based on self-reported scores on the ED 100 K and the EDE-Q.

Results

Mean PHQ-9 total score for those with a previous history of ED was 10.67 (SD 6.33), for those with a current ED 16.61 (SD 5.84), and for those with no lifetime history of ED 6.83 (SD 5.58). Excellent internal consistency was demonstrated by Cronbach’s alpha’s for individuals with a previous ED (.88), for individuals with a current ED (.86), and for individuals with no history of ED (.88). Acceptable convergent validity was indicated based on significant correlations between the PHQ-9 and GAD-7 and DERS-SF. Confirmatory Factor Analyses revealed a mediocre fit for a one-factor structure of the PHQ-9, regardless of diagnostic status.

Conclusions

The psychometric properties of the Norwegian version of the PHQ-9 are acceptable across females with and without ED, and the PHQ-9 can be recommended for use in clinical ED settings and for people without mental disorders.